TY - JOUR. T1 - Diagnostic refinement of chronic myeloproliferative disorders and thrombocytoses of unknown origin by multiple RT-PCR and capillary electrophoresis of BCR-ABL rearrangements and JAK2 (V617F) mutation. AU - Ammatuna, Emanuele. AU - Ottone, Tiziana. AU - Zaza, Serena. AU - Lavorgna, Serena. AU - Grillo, Rosa. AU - Curzi, Paola. AU - Panetta, Paola. AU - Federici, Giorgio. AU - Amadori, Sergio. AU - Lo-Coco, Francesco. PY - 2007/5. Y1 - 2007/5. N2 - Detection of genetic markers improves diagnostic refinement of chronic myeloproliferative disorders (CMDs) and is helpful in discriminating reactive conditions mimicking CMDs such as reactive erythrocytosis and thrombocytosis. We set-up a multiplex real-time polymerase chain reaction assay followed by capillary electrophoresis, designed to simultaneously screen the two main genetic lesions associated with CMDs, i.e. the BCR-ABL fusion characteristic of chronic myeloid leukemia and the JAK2 V617F mutation that characterises polycythaemia ...
TY - JOUR. T1 - Prenatal diagnosis of a transient myeloproliferative disorder in trisomy 21. AU - Baschat, A. A.. AU - Wagner, T.. AU - Malisius, R.. AU - Gembruch, U.. PY - 1998/7/1. Y1 - 1998/7/1. N2 - We report the prenatal diagnosis of a transient myeloproliferative disorder suggestive of leukaemia in a fetus with hepatosplenomegaly, hydrops and 47,XY,+21 karyotype. The initial fetal white blood cell count at 26 + 5 weeks gestation was 190/nl with 70 per cent blast cells. Immunophenotyping of the large blasts revealed surface markers suggestive of an early stem cell differentiation arrest resulting in undifferentiated polyclonal myelopoiesis. The fetal heart tracing showed minimal beat-to-beat variability in the presence of high leukocyte counts. Serial fetal blood sampling showed decreasing blast cells in the peripheral blood and normalization of white blood cell counts. Although there was increasing hydrops, this period was marked by improvement of the fetal heart rate pattern. Finally ...
Background: This study was conducted to evaluate the frequency of JAK2, CALR and MPL mutations in with BCR-ABL myeloproliferative neoplasms and their association with demographic data and hematologic parameters in a referral center, in the Middle East. Methods: Seventy-one patients with BCR-ABL negative myeloproliferative neoplasms were evaluated for JAK2 V617F, CALR type 1, type 2, and MPL by allele-specific PCR and conventional PCR from 2018 to 2019. Results: Twenty three patients were categorized as polycythemia vera and demonstrated JAK2 V617F in 91.3 % of these cases. Thirty-eight patients were classified as essential thrombocythemia and showed JAK2 V617F in 52.6%, CALR type 1 in 18.4%, CALR type 2 in 7.9% and no mutation in 21.1%. Seven patients were recognized as primary myelofibrosis and exhibited JAK2 V617F mutation in 57.1%, CALR type 1 in 14.3 %, CALR type 2 in 14.3% and no mutation in 14.3%. Three patients were diagnosed as MPN, unclassifiable and revealed JAK2 V617F mutation in 33.3% and
Previous small studies and clinical cases have suggested a possible association between pulmonary hypertension (PH) and chronic myeloproliferative disorders (CMPD). MPD may cause PH through different mechanisms as: high cardiac output, asplenia, direct obstruction of pulmonary arteries by megakaryocytes, chronic thromboembolic endothelial pulmonary hypertension (CTEPH), porto-pulmonary hypertension (POPH). However, the exact prevalence of PH in this group of disorders is not known.. This study is designed to identify the pulmonary vascular changes and describe the prevalence of pulmonary hypertension (defined in this study as mean pulmonary arterial hypertension (mPAP) ≥25mmHg as assessed by right-heart catheterization (RHC) or systolic pulmonary arterial pressure (sPAP) ≥37mmHg (2.9 m/s) assessed by echocardiography. ...
Chronic myeloproliferative disorders are a group of slow-growing blood cancers in which the bone marrow makes too many abnormal red blood cells, white blood cells, or platelets, which accumulate in the blood. The type of myeloproliferative disorder is based on whether too many red blood cells, white blood cells, or platelets are being made. Sometimes the body will make too many of more than one type of blood cell, but usually one type of blood cell is affected more than the others are ...
The PRV-1 gene has been proposed as a marker of polycythaemia vera (PV). PRV-1 and NB1 are alleles of the polymorphic gene CD177, which belongs to the Ly-6/uPAR superfamily, and their coding regions differ at only four nucleotides. We studied neutrophil CD177 mRNA levels in normal subjects and in 235 patients with Ph-negative chronic myeloproliferative disorders (CMD), including PV, essential thrombocythaemia and myelofibrosis with myeloid metaplasia. Additional disease states were investigated for comparison. Highly variable neutrophil CD177 mRNA levels were observed in normal individuals. Neutrophils isolated from the bone marrow, or from peripheral blood following granulocyte colony-stimulating factor administration showed markedly higher CD177 expression than circulating granulocytes on steady state. Increased neutrophil CD177 mRNA levels were detected in all CMD. Elevated values were also found in reactive conditions and in disorders such as chronic myeloid leukaemia and myelodysplastic ...
The chronic myeloproliferative disorders (CMPD) are a group of clinically related diseases characterized by clonal hematopoiesis with increased proliferation of one or more myeloid cell lineages. The identification of JAK2 mutations (JAK2V617F and JAK2 exon 12) in patients with CMPD is of great significance in the understanding of the molecular mechanisms underlined the pathogenesis of the disease contributing also to clinical management of patients. However, the precise pathogenetic contribution of JAK2 mutation is far from being fully elucidated and it is currently under intense investigation. Testing of JAK2 mutations has made the diagnosis of CMPD more precise than ever before, while genotype-phenotype associations have been identified. Furthermore, the discovery of JAK2 mutations facilitated the development of new targeted therapies and clinical trials are currently ongoing.
In this issue of the Hematology, Transfusion and Cell Therapy Journal, Cacemiro et al. evaluated the plasma cytokine profile of 47 patients with Ph-negative myeloproliferative neoplasms (MPN) [essential thrombocythemia (ET), primary myelofibrosis (PMF), and polycythemia vera (PV)] and of healthy subjects.1 They demonstrated increased levels of pro-inflammatory cytokines in MPN patients and higher levels of interferon (IFN)-γ-induced protein 10 (IP-10) in PMF patients with the JAK2 V617F mutation. They found differences in the cytokine profile among the three MPN disorders, including increased levels of IL-12p70, IL-17A, and RANTES in PMF, showing that MPN, in particular PMF, have altered inflammatory profiles. However, their sample population did not make clinical and prognostic implications of their findings possible.. What is the clinical relevance of the altered cytokine levels in MPN? Are they related to constitutional symptoms, transformation or evolution to fibrosis? Do they have an ...
Children with Down syndrome (DS) up to the age of 4 years are at a 150-fold excess risk of developing myeloid leukemia (ML-DS). Approximately 4%-5% of newborns with DS develop transient myeloproliferative disorder (TMD). Blast cell structure and immunophenotype are similar in TMD and ML-DS. A mutation in the hematopoietic transcription factor GATA1 is present in almost all cases. Here, we show that simple techniques detect GATA1 mutations in the largest series of TMD (n = 134; 88%) and ML-DS (n = 103; 85%) cases tested. Furthermore, no significant difference in the mutational spectrum between the 2 disorders was seen. Thus, the type of GATA1 sequence mutation is not a reliable tool and is not prognostic of which patients with TMD are probable to develop ML-DS.
The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek.[1] In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from myeloproliferative diseases to myeloproliferative neoplasms.[2] This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.. The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.. ...
8p11 myeloproliferative syndrome (EMS) is a very rare clinicopathological entity which is characterized by the appearance of a myeloproliferative neoplasm in the bone marrow, peripheral lymphadenopathy, usually caused by T or B lymphoblastic lymphoma/leukemia, and a reciprocal translocation involving chromosome 8p11. Herein we describe a 22-year-old male patient with unusual clinical presentation of EMS. Namely, he initially presented with prolonged epistaxis. Complete blood count showed elevated hemoglobin (17.7g/dl), thrombocytopenia (98x109/l) and leukocytosis (57x109/l). Bone marrow aspirate and biopsy findings corresponded with the presence of a myeloproliferative neoplasm while cytogenetic analysis revealed t(8;13)(p11q12). After that ZMYM2-FGFR1 in-frame fusion was confirmed at the molecular level. Immediately after establishing the diagnosis of a myeloproliferative neoplasm (MPN) generalized lymphadenopathy was developed. Histopathologic examination of lymph node sample confirmed the ...
TY - JOUR. T1 - Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage. AU - Ren, Mingqiang. AU - Tidwell, Josephine A.. AU - Sharma, Suash. AU - Cowell, John Kenneth. PY - 2012/6/6. Y1 - 2012/6/6. N2 - Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19+ IgM- CD43+ immunophenotype was seen both in primary tumors and two cell lines derived from ...
Mutations in JAK2, MPL and CALR are highly relevant to the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs). We performed high resolution melting analysis and Sanger sequencing together with T-A cloning to elucidate the unique mutation profile of these genes, in Chinese patients with MPNs. Peripheral blood DNA samples were obtained from 80 patients with polycythemia vera (PV), 80 patients with essential thrombocytosis (ET) and 50 patients with primary myelofibrosis (PMF). Ten PV patients were identified with diverse JAK2 exon 12 mutations. Five novel JAK2 Exon 12 mutation patterns (M532V/E543G, N533D, M535I/H538Y/K549I, E543G and D544N) were described. JAK2 V617F was detected in 140 samples (66 PV, 45 ET and 29 PMF). JAK2 Exon 12 mutations were prevalent (13%) and variable in the Chinese patients. Compared with PV patients with JAK2 V617F mutations, PV patients with JAK2 exon 12 mutations had an earlier median onset of disease (P = 0.0013). MPL W515L/K mutations were ...
Abraham S, Salama M, Hancock J, Jacobsen J, Fluchel M. Congenital and childhood myeloproliferative disorders with eosinophilia responsive to imatinib. Pediatr Blood Cancer. 2012;59(5):928-9.. Bauer JD, Capra S. Nutrition intervention improves outcomes in patients with cancer cachexia receiving chemotherapy -- a pilot study. Support Care Cancer. 2005;13(4):270-4.. Bell DR, Gochenaur K. Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. J Appl Physiol. 2006;100(4):1164-70.. Bruchova H, Merkerova M, Prchal JT. Aberrant expression of microRNA in polycythemia vera. Haematologica. 2008;93(7):1009-16.. Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea--a review. J Am Coll Nutr. 2006;25(2):79-99.. Chen F, Li L, Ma D, et al. Imatinib achieved complete cytogenetic response in a CML patient received 32-year indirubin and its derivative treatment. Leuk Res. 2010 Feb;34(2):e75-7.. de Lacerda JF, Oliveira SN, Ferro JM. Chronic myeloproliferative diseases. Handb Clin ...
Complications of Myelodysplastic/myeloproliferative disease including hidden complications, secondary medical conditions, symptoms, or other types of Myelodysplastic/myeloproliferative disease complication.
Myeloproliferative diseases were first described by William Dameshek in 1951. In 2008, the World Health Organization established a new classification system and introduced the term myeloproliferative neoplasms (MPNs). Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are the most prevalent MPNs and are characterized by overproduction of leukocytes, erythrocytes, or platelets; development of bone marrow fibrosis; leukemic transformation; and arterial and venous thrombosis. When Dameshek proposed the term myeloproliferative diseases, he also proposed the presence of a then-undiscovered stimulus that drove proliferation. We now understand that mutation of the JAK2 gene, JAK2 V617F, is the most common stimulus, occurring in 95% of patients with PV and 60% of those with ET or PMF. Myeloproliferative neoplasms are relatively rare; are acquired in middle to older age; and are, despite their classification as neoplasms, indolent diseases, with survival measured ...
Conclusions:. Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms. ...
Classic BCR-ABL negative chronic myeloproliferative neoplasms (MPN) are stem cell disorders characterized by abnormal myeloid proliferation and increased blood cell counts and comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF).. Myeloproliferative neoplasms (MPN) are common malignancies in elderly individuals as the combined annual incidence rates of classical MPNs were reported to be 0.84, 1.03, and 0.47 per 100,000 respectively for PV, ET, and PMF but with a wide variation in prevalence rates reported in different studies. The 5-year relative survival rates are 84.8, 89.9, and 39% for PV, ET and PMF patients, respectively.. Thromboembolic complications represent a major cause of morbidity and mortality in MPN, particularly in PV and ET. The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood.. Several pathophysiological mechanisms help explain the increased likelihood of ...
TY - JOUR. T1 - Practical management of classical myeloproliferative disorder patients. T2 - A clinicians guide. AU - Mesa, Ruben A.. PY - 2006/8/1. Y1 - 2006/8/1. N2 - The classical myeloproliferative disorders (MPDs) are comprised of the clonal, BCR-ABL-negative, chronic myelold disorders of essential thrombocythemia, polycythemia vera, and myelofibrosis with myeloid metaplasia. Managment of these disorders remains a significant challenge due to the varied range of prognosis and phenotypic manifestations. Curative therapy, achieved in some patients through allogeneic stem cell transplantation, is elusive or inappropriate in most. Additionally, no available medical therapy has been shown to clearly improve survival or delay disease progression. Current management involves an emphasis on prevention of thrombohemorrhagic complications (through aspirin treatment, phlebotomy and cytoreduction in high-risk patients) in early-stage patients and symptomatic care in those with advanced disease. ...
Myeloproliferative Neoplasms (MPNs): Diagnosis, Treatment and Side Effects Management This continuing education virtual lecture on myeloproliferative neoplasms diagnosis, treatment and side effects management is for nurses, nurse practitioners, and oncology social workers. Topics covered include types of myeloproliferative neoplasms tests for diagnosis, treatments and management of side effects.The material is presented by a physician, a pharmacist and a nurse practitioner. There is no fee for this educational activity.
Know more about the symptoms, causes, diagnosis and treatment for Myeloproliferative Neoplasms. mfine has the finest of Oncologist who will provide the best treatment.
TY - JOUR. T1 - Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk. AU - Staser, Karl. AU - Park, Su Jung. AU - Rhodes, Steven D.. AU - Zeng, Yi. AU - He, Yong Zheng. AU - Shew, Matthew A.. AU - Gehlhausen, Jeffrey R.. AU - Cerabona, Donna. AU - Menon, Keshav. AU - Chen, Shi. AU - Sun, Zejin. AU - Yuan, Jin. AU - Ingram, David A.. AU - Nalepa, Grzegorz. AU - Yang, Feng Chun. AU - Clapp, D. Wade. PY - 2013/1/2. Y1 - 2013/1/2. N2 - Neurofibromatosis type 1 (NF1) predisposes individuals to the development of juvenile myelomonocytic leukemia (JMML), a fatal myeloproliferative disease (MPD). In genetically engineered murine models, nullizygosity of Nf1, a tumor suppressor gene that encodes a Ras-GTPase-activating protein, results in hyperactivity of Raf/Mek/Erk in hematopoietic stem and progenitor cells (HSPCs). Activated Erk1/2 phosphorylate kinases and transcription factors with myriad mitogenic roles in diverse cell types. However, genetic studies examining ...
The 8p11 myeloproliferative syndrome is an aggressive neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 tyrosine kinase gene on chromosome 8p11-12. By our count, 65 cases are currently reported in the literature. This neoplasm affects patients of a …
CHROMOSOME 8p11 MYELOPROLIFERATIVE SYNDROME description, symptoms and related genes. Get the complete information in our medical search engine for phe
Abstract Background and Objectives Chronic myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders. They are heterogeneous in symptoms and mainly consist of Philadelphia chromosome positive (Ph+) and negative (Ph-). The Ph- group includes polycythemia Vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and other rare disorders. In the latter ...
The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival (OS), and mutational status of the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) genes. We compared hematologic and clinical features of JAK2V617F-ET vs. CALR-mutated ET vs. JAK2V617F-PV patients. JAK2V617F-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to CALR-mutated patients (p , 0.05). The mutant allele burden in JAK2V617F-PV and JAK2V617F-ET ...
Copy For Citation Kabukcuoolu S. AMERICAN JOURNAL OF SURGICAL PATHOLOGY, vol.24, no.10, pp.1437, 2000 (Journal Indexed in SCI) ...
This study is investigating the efficacy and tolerability of givinostat [Italfarmaco] in the treatment of patients with JAK2V617F positive, chronic
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Bulgular: JAK-2 mutasyonu PV li hastalar n %86 s nda, ET li hastalar n %51,5 inde ve PMF li hastalar n %50,4 nde pozitif bulundu. Tan da tromboz ve kanama, PV li hastalar n s ras yla %20,6 ve %7,5 inde, ET li hastalar n %15,1 ve %9 unda ve PMF li hastalar n %9,5 ve %10,4 nde saptand . Alt y z sekiz hasta (%85,9) sitored ktif tedavi alm t . En s k kullan lan ila hidroksi re (%89,6) idi. L semik ve fibrotik transformasyon s kl %0,6 ve %13,2 idi. 10 y ll k hesaplanan toplam sa kal m PV, ET ve PMF hastalar nda s ras yla %89,7, %85 ve %82,5 idi. 10 y ll k toplam sa kal m a s ndan ET, PV ve PMF hastalar nda anlaml fark yoktu ...
Bulgular: leri ya , tan da y ksek l kosit say s JAK2 mutasyon pozitifli i tromboz i in risk fakt r olarak bulunmu tur. Trombosit say m n n 1000x109/L zerinde olmas kanama komplikasyonlar a s ndan risk fakt r d r. Hidroksi re tedavisi l semik d n mle ili kili bulunmam t r. Bu hastalarda: Medyan takip s resi 50 ay (22,2- 81,75 eyrekler) idi. Primer miyelofibrozisli hastalar ET i in 179 ay ve PV i in 231 ay olan ya am s releri ile kar la t r ld nda 137 ay ile en k sa ya am s resine sahip hastalard r. L semik transformasyon, tromboembolik olaylar, 60 ya st olmak ve anemi ya am s resinin etkileyen fakt rler olarak bulunmu tur ...
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Following the success of imatinib in BCR-ABL positive CML and its capacity to occupy the ATP binding sites of several other tyrosine kinases such as ARG (ABL2), KIT, PDGFRA, PDGFRB or FMS, there has been considerable interest in extending its clinical use to diseases in which other activated tyrosine kinases are implicated. In this issue Baccarani et al.27 present the results of a phase-II-trial in which patients with FIP1L1-PDGFRA-positive CEL or HES without a known molecular target were treated with imatinib at a target dose of 400 mg/day. This is the largest such study reported to date and has the advantage of relatively long follow-up. Based on the high rates of rapid complete hematologic remissions previously reported by other groups,27 it is not surprising that all FIP1L1-PDGFRA positive patients achieved complete hematologic remissions after a median of 2 months. In addition, all patients achieved complete molecular remission, as determined by nested RT-PCR, after a median of 6 months, ...
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TY - JOUR. T1 - Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms. AU - Nischal, Sangeeta. AU - Bhattacharyya, Sanchari. AU - Christopeit, Maximilian. AU - Yu, Yiting. AU - Zhou, Li. AU - Bhagat, Tushar D.. AU - Sohal, Davendra. AU - Will, Britta. AU - Mo, Yongkai. AU - Suzuki, Masako. AU - Pardanani, Animesh. AU - Michael McDevitt, McDevitt. AU - Maciejewski, Jaroslaw P.. AU - Melnick, Ari M.. AU - Greally, John M.. AU - Steidl, Ulrich. AU - Moliterno, Alison R. AU - Verma, Amit. PY - 2013/2/1. Y1 - 2013/2/1. N2 - Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis than essential thrombocytosis or polycythemia vera, the molecular distinctions between these subgroups are not well elucidated. We conducted the HELP (HpaII tiny fragment enriched ...
Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new Dynamic International Prognostic Scoring System ...
TY - JOUR. T1 - Molecular diagnosis of myeloproliferative neoplasms. AU - Patnaik, Mrinal M.. AU - Tefferi, Ayalew. PY - 2009/7/1. Y1 - 2009/7/1. N2 - The molecular profiling of myeloproliferative neoplasms (MPNs) has introduced a paradigm shift in the process of diagnosis, prognostication, monitoring and treatment of these diseases. The discovery of the BCR-ABL fusion oncogene is an example of a remarkable bench-to-bedside story. It has provided a comprehensive explanation of the pathogenesis of chronic myelogenous leukemia, and has resulted in the development of excellent treatment strategies. It has led to the use of advanced diagnostic techniques, such as fluorescence in situ hybridization and PCRs that allow for more effective means to monitor disease treatment, including the detection of minimal residual disease, early relapse and drug resistance. Unlike chronic myelogenous leukemia, the exact molecular pathways for the BCR-ABL-negative MPNs have not been completely elucidated. The ...
This is a concise, practical, case-based book documenting examples and scenarios that will help you manage challenging clinical issues for patients with myeloproliferative neoplasms. The editors and authors have strived to distil the very latest information in this rapidly advancing field in a way that will help you to update your practice and manage your patients. The key focuses are: diagnosis, both standard and challenging; both day-to-day management as well as special situations such as surgery, thrombotic events and pregnancy; and finally, managing evolving situations with MPN such as progression to acute myeloid leukemia. This book is an outstanding resource that includes a discussion of both classical myeloproliferative neoplasms, such as essential thrombocythemia, polycythemia vera and myelofibrosis, and also less common disorders such as systemic mast cell disease, hypereosinophilia, MPN/MBS overlap syndromes and atypical CML, amongst others. This book is a practical reference for ...
BACKGROUND Hematopoietic malignancies are a group of blood cell disorders characterized by abnormal hematopoietic proliferation. OBJECTIVE The identification of specific clinicopathologic characteristics and tumor-related gene status provides critical information on potential therapeutic targets. METHODS The specimens were tested with immunohistochemistry, flow cytometry, RT-PCR and fragment analysis. RESULTS In this study, a patient with a long history of tobacco use was reported with a diagnosis of simultaneous low-grade B-cell lymphoproliferative disorder (LPD) and myeloproliferative neoplasm (MPN). Mutational analysis revealed that JAK2 V617F mutation and CALR mutation with 52bp deletion were present in this patient. CONCLUSION These results suggest that lymphoproliferative and myeloproliferative neoplasms may coexist, although the pathogenetic mechanism of coexisting hematologic requires further investigation. Additionally, the data indicate that JAK2 V617F and CALR mutations are not
ETV6-ABL1 is a rare gene fusion with oncogenic properties, reported so far in 28 patients presenting a variety of haematological malignancies associated with clinical outcome, including chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and chronic myeloproliferative neoplasm (cMPN). Here we report on a 46-year-old female who presented with Philadelphia negative CML, positive for the ETV6-ABL1 fusion. Whole genome screening carried out with oligonucleotide arrays showed a subtle loss at 12p13 and cryptic imbalances within the 9q34.3 region in a highly unstable genome. FISH mapping with custom BAC probes identified two breakpoints 5 Mb apart within the 9q34 region, together with a break at 12p13. While FISH with commercial BCR-ABL1 probes failed to detect any ABL1 changes, the ETV6 break-apart probe conclusively identified the ETV6-ABL1 fusion thus determining the probes role as the primary diagnostic FISH test for this chimeric oncogene. In addition, we
PURPOSE Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy.. PATIENTS AND METHODS. The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers.. RESULTS MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P , .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 ...
Title: Molecular Pathogenesis of Philadelphia-Positive Chronic Myeloid Leukemia - is it all BCR-ABL?. VOLUME: 11 ISSUE: 1. Author(s):H. Rumpold and G. Webersinke. Affiliation:Department of Haematology and Medical Oncology, Hospital Barmherzige Schwestern Linz, Seilerstaette 4, 4010 Linz, Austria.. Keywords:BCR-ABL, CML, pathogenesis, molecular genetics, chronic myeloproliferative diseases, Chronic Myelogenous Leukemia, Leukemia, Mastocytosis, diagnostic, chromosome, oncogen, stem cells, MOLECULAR BIOLOGY, cytoplasm, tyrosine kinase, plekstrine homology domain, toxin substrate, phosphorylation of tyrosine, immune system, bone marrow cells, haematopoiesis, pulmonary haemorrhages, PH-TRANSLOCATION, risk factor, phenotype, heterozygous, myeloproliferative nepolasms, myeloid colony, phenylalanine, leukemic cell, cell, phosphorylation, antiapoptotic protein, michochondrial cytochrome-c, mRNA, disease progression, Granulocytemacrophage progenitor cells, mutation rate, clonogenicity potential, STEM ...
BACKGROUND: Cancers result from the accumulation of somatic mutations, and their properties are thought to reflect the sum of these mutations. However, little is known about the effect of the order in which mutations are acquired. METHODS: We determined mutation order in patients with myeloproliferative neoplasms by genotyping hematopoietic colonies or by means of next-generation sequencing. Stem cells and progenitor cells were isolated to study the effect of mutation order on mature and immature hematopoietic cells. RESULTS: The age at which a patient presented with a myeloproliferative neoplasm, acquisition of JAK2 V617F homozygosity, and the balance of immature progenitors were all influenced by mutation order. As compared with patients in whom the TET2 mutation was acquired first (hereafter referred to as TET2-first patients), patients in whom the Janus kinase 2 (JAK2) mutation was acquired first (JAK2-first patients) had a greater likelihood of presenting with polycythemia vera than with
The DRG code for MYELOPROLIFERATIVE DISORDERS OR POORLY DIFFERENTIATED NEOPLASMS WITH MAJOR O.R. PROCEDURE WITHOUT CC/MCC is 828. DRG code 828 is classified under DRG code range Myeloproliferative Diseases & Disorders, Poorly Differentiated Neoplasms.
Myeloproliferative Neoplasm Causes, Types, Treatment, Symptoms & Signs. Click for basic information about myeloproliferative neoplasm, its symptoms and treatment.
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Rearrangements of the genes for the platelet-derived growth factor receptor alpha (PDGFRa) or the platelet-derived growth factor receptor beta (PDGFRβ) have been identified in myeloid/lymphoid neoplasms with eosinophilia.1 Fusions of PDGFRβ, which encodes a type III receptor tyrosine kinase, result in constitutive kinase activation and promotion of survival, proliferation and cell migration.2 Since the description of ETV6-PDGFRβ in 1994,3 more than 30 PDGFRβ fusion partners have been described, most of which have been identified in myeloproliferative neoplasms or in a myelodysplastic syndrome/myeloproliferative neoplasm overlap, but only rarely in acute myeloid leukemia (AML).541. PDGFRβ fusions are commonly in-frame mutations that contain an N-terminal fusion partner with dimerization/oligomerization motifs, enabling PDGFR-ligand-independent receptor tyrosine kinase activation.61 PDGFRβ-rearranged chronic myeloproliferative neoplasms show a favorable response to imatinib with a 10- year ...
New research from Karolinska Institutet shows that the survival for patients with chronic myeloproliferative diseases has improved in recent decades. This is despite the fact that no targeted drugs have yet been registered for this group of diseases. More than 9,000 patients have been included in a unique population-based study which has been published in the Journal of Clinical Oncology.
The recent discovery of an acquired activating point mutation in JAK2, substituting valine at amino acid position 617 for phenylalanine, has greatly improved our understanding of the molecular mechanism underlying chronic myeloproliferative neoplasms. Strikingly, the JAK2V617F mutation is found in nearly all patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia and primary myelofibrosis. Thus, JAK2 represents a promising target for the treatment of myeloproliferative neoplasms and considerable efforts are ongoing to discover and develop inhibitors of the kinase. Here, we report potent inhibition of JAK2V617F and JAK2 wild-type enzymes by a novel substituted quinoxaline, NVP-BSK805, which acts in an ATP-competitive manner. Within the JAK family, NVP-BSK805 displays more than 20-fold selectivity towards JAK2 in vitro, as well as excellent selectivity in broader kinase profiling. The compound blunts constitutive STAT5 phosphorylation ...
Myelodysplastic/myeloproliferative neoplasms are a group of diseases in which the bone marrow makes too many white blood cells. Myelodysplastic /myeloproliferative neoplasms are diseases of the blood and bone marrow. Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone...
Myelodysplastic/myeloproliferative neoplasms are a group of diseases in which the bone marrow makes too many white blood cells. Myelodysplastic /myeloproliferative neoplasms are diseases of the blood and bone marrow. Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone...
TY - JOUR. T1 - Somatic mutations of calreticulin in myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms. AU - Malcovati, Luca. AU - Rumi, Elisa. AU - Cazzola, Mario. PY - 2014/11/1. Y1 - 2014/11/1. UR - http://www.scopus.com/inward/record.url?scp=84908457975&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84908457975&partnerID=8YFLogxK. U2 - 10.3324/haematol.2014.113944. DO - 10.3324/haematol.2014.113944. M3 - Article. C2 - 25420280. AN - SCOPUS:84908457975. VL - 99. SP - 1650. EP - 1652. JO - Haematologica. JF - Haematologica. SN - 0390-6078. IS - 11. ER - ...
Genetics Home Reference : 25 8p11 myeloproliferative syndrome is a blood cancer that involves different types of blood cells. Blood cells are divided into several groups (lineages) based on the type of early cell from which they are descended. Two of these lineages are myeloid cells and lymphoid cells. Individuals with 8p11 myeloproliferative syndrome can develop both myeloid cell cancer and lymphoid cell cancer ...
Human myeloproliferative disorders form a range of clonal haematological malignant diseases, the main members of which are polycythaemia vera, essential thrombocythaemia, and idiopathic myelofibrosis. The molecular pathogenesis of these disorders is unknown, but tyrosine kinases have been implicated in several related disorders. We investigated the role of the cytoplasmic tyrosine kinase JAK2 in patients with a myeloproliferative disorder.We obtained DNA samples from patients with polycythaemia vera, essential thrombocythaemia, or idiopathic myelofibrosis. The coding exons of JAK2 were bidirectionally sequenced from peripheral-blood granulocytes, T cells, or both. Allele-specific PCR, molecular cytogenetic studies, microsatellite PCR, Affymetrix single nucleotide polymorphism array analyses, and colony assays were undertaken on subgroups of patients.A single point mutation (Val617Phe) was identified in JAK2 in 71 (97%) of 73 patients with polycythaemia vera, 29 (57%) of 51 with essential
Human myeloproliferative disorders form a range of clonal haematological malignant diseases, the main members of which are polycythaemia vera, essential thrombocythaemia, and idiopathic myelofibrosis. The molecular pathogenesis of these disorders is unknown, but tyrosine kinases have been implicated in several related disorders. We investigated the role of the cytoplasmic tyrosine kinase JAK2 in patients with a myeloproliferative disorder.We obtained DNA samples from patients with polycythaemia vera, essential thrombocythaemia, or idiopathic myelofibrosis. The coding exons of JAK2 were bidirectionally sequenced from peripheral-blood granulocytes, T cells, or both. Allele-specific PCR, molecular cytogenetic studies, microsatellite PCR, Affymetrix single nucleotide polymorphism array analyses, and colony assays were undertaken on subgroups of patients.A single point mutation (Val617Phe) was identified in JAK2 in 71 (97%) of 73 patients with polycythaemia vera, 29 (57%) of 51 with essential
Disorders which share common features: Polycythemia Vera causes the overproduction of red cells, white cells and platelets; Idiopathic Myelofibrosis has an overproduction of white cells or platelets with anemia and an increase in bone marrow fibrous tissue. Essential Thrombocytosis features an increase in circulating platelets. Also Chronic Neutrophilic Leukemia and Chronic Eosinophilic Leukemia both which may develop into Leukemia.
Myelophthisic anemia (or myelophthisis) is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue either by fibrosis, tumors or granulomas. The word comes from the roots myelo-, which refers to bone marrow, and phthysis, shrinkage or atrophy. Myelophthisis can occur in the setting of chronic myeloproliferative disease (e.g. myelofibrosis), leukemia, lymphoma, and metastatic carcinoma or myeloma. It is common in people who have chronic idiopathic myelofibrosis. It has been linked to small-cell lung cancer, breast cancer or prostate cancer that metastasizes to the bone marrow. Historically, the most common cause of displacement of healthy bone marrow was tuberculosis.[citation needed] Currently, the most common cause is displacement of bone marrow by metastatic cancer (extramedullary hematopoiesis tends to be modest). Other causes include myeloproliferative disorders (especially late-stage ...
RESULTS: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies ...
Kremyanskaya M, Najfeld V, Mascarenhas J, Hoffman R. The polycythemias. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice . 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 67. National Cancer Institute: PDQ Chronic Myeloproliferative Neoplasms Treatment: Polycythemia Vera. Bethesda, MD: National Cancer Institute. Date last modified December 3, 2014. Available at: www.cancer.gov/cancertopics/pdq/treatment/myeloproliferative/HealthProfessional/page3. Accessed March 3, 2015.. Tefferi A. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In: Goldman L, Schafer AI, eds. Goldmans Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 166. ...
Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9.0 mutations in 100.0 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load | 50.0%) was predominantly observed
This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canadas national genomics strategy with funding from the federal government. Maintenance, support, and commercial licensing is provided by OMx Personal Health Analytics, Inc. Designed by Educe Design & Innovation Inc. ...
Kremyanskaya M, Najfeld V, Mascarenhas J, Hoffman R. The polycythemias. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018:chap 68. National Cancer Institute website. Chronic myeloproliferative neoplasms treatment (PDQ) -- health professional version. www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#link/_5. Updated February 1, 2019. Accessed March 1, 2019. Tefferi A. Polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 166. BACK TO TOP Review Date: 1/29/2019 Reviewed By: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.. ...
Research in the Jerry Spivak Lab focuses on chronic myeloproliferative disorders, particularly their molecular mechanisms and methods for distinguishing them diagnostically and interventionally. By analyzing gene expression in polycythemia vera stem cells, we have learned that patients with polycythemia vera can be differentiated from those with erythrocytosis and can be diagnosed as having either aggressive or slow-growing disease. We are also studying the roles played by specific molecular markers in the pathogenesis and diagnosis of polycythemia vera.. Research Areas: stem cells, pathogenesis, polycythemia vera, myeloproliferative disorders ...
Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F(-) patients and a single V617F(+) patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F(+) ET patients, those with MPL mutations displayed lower hemoglobin and higher platelet levels at diagnosis, higher serum erythropoietin levels, endogenous megakaryocytic but
JA Denburg, WE Wilson, J Bienenstock; Basophil production in myeloproliferative disorders: increases during acute blastic transformation of chronic myeloid leuk
TY - JOUR. T1 - Idiopathic myelofibrosis. T2 - dental treatment considerations.. AU - Steelman, Robert. AU - Holmes, D.. AU - Cranston, R.. AU - Cupp, D.. PY - 1991/3. Y1 - 1991/3. N2 - Idiopathic myelofibrosis is a myeloproliferative disorder of unknown origin. The bone marrow becomes fibrotic with an associated decrease in hematopoiesis resulting in anemia, bleeding problems, splenomegaly, and other secondary abnormalities. Although idiopathic myelofibrosis is usually diagnosed in middle age, there have been a few reports of the disorder in the pediatric population. This case report documents dental treatment considerations in a 6-year-old female with idiopathic myelofibrosis, severe anemia, and abnormal blood coagulation studies. The patient was successfully treated in a hospital after medical consultation, transfusion of packed red blood cells, and administration of prophylactic antibiotics. Local hemostatic measures following multiple extractions of carious teeth controlled bleeding. No ...
BACKGROUND: The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of these mutations has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for these mutations in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms ...
The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2 V617F and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for ...
Dates: October 12-14, 2017Location: Budapest, HungaryChairs: C Harrison, JJ Kiladjian EHA and the EHA Scientific Working Group on Myeloproliferative Neoplasms are organizing this EHA-SWG Scientific Meeting on Challenges in the Diagnosis and Management of ...
Polycythemia vera (PV) is a chronic myeloproliferative disorder that can evolve to marrow fibrosis or acute leukemia (AML). Cytogenetic alterations can be detected in around 25% of patients at diagnosis and in up to 50% of those with progression. We report a case of PV with evolution to AML in which it was possible to demonstrate the two-hit model of leukemogenesis: one mutation confers proliferative advantage and another interferes with differentiation. Case: A 55-year-old female patient was diagnosed with PV in 2002 and treated with phlebotomies and hydroxyurea. In 2006, there was progression topost-polycythemic fibrosis with AML one year later. She presented the JAK2V617F mutation. The result of karyotyping performed at diagnosis was normal and at transformation, 46,XX,del(20)(q13.1) was detected in 4/20 metaphases. FISH analysis of a stored sample for 20q13 showed the deletion in 20% of interphases confirming the earlier presence of a clonal abnormality that was not detected by karyotyping. ...
Collectively, the studies discussed demonstrate that occasional patients with CALR mutation-positive essential thrombocythemia or myelofibrosis carry other myeloproliferative neoplasms-initiating genetic mutations (including JAK2 V617F), acquire secondary mutations before or after the CALR mutation, or evolve over time to being CALR mutation-homozygous.. Br J Haematol ...
Oncogenic ras alleles are among the most common mutations found in patients with acute myeloid leukemia (AML). Previously, the role of oncogenic ras in cancer was assessed in model systems overexpressing oncogenic ras from heterologous promoters. However, there is increasing evidence that subtle differences in gene dosage and regulation of gene expression from endogenous promoters play critical roles in cancer pathogenesis. We characterized the role of oncogenic K-ras expressed from its endogenous promoter in the hematopoietic system using a conditional allele and IFN-inducible, Cre-mediated recombination. Mice developed a completely penetrant myeloproliferative syndrome characterized by leukocytosis with normal maturation of myeloid lineage cells; myeloid hyperplasia in bone marrow; and extramedullary hematopoiesis in the spleen and liver. Flow cytometry confirmed the myeloproliferative phenotype. Genotypic and Western blot analysis demonstrated Cre-mediated excision and expression, ...
30 REPRESENTATIVE TEST QUESTIONS FROM PREVIOUS EXAMINATIONS Including answers, in each question only one answer is correct 1 Which of the following bone marrow diseases is considered a chronic myeloproliferative disorder a b c d e Chronic myelomonocytic leukaemia Essential thrombocythaemia Hypocellular myelodysplastic syndrome Juvenile chronic myeloid leukaemia Refractory anaemia with excess of blasts in…
Ruxolitinib (Jakafi), an oral JAK1 and JAK2 kinase inhibitor, was approved in November 2011 for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.14 Two phase III trials demonstrated significant improvement compared with best available therapy for spleen size, symptoms, and burden reduction, as well as for quality of life.14-16 However, the reduced spleen size was not shown to be consistently durable in a phase I/II study and neither phase III study reported a significant survival benefit.17,18 This agent is commonly associated with hematologic side effects; anemia was reported in 96% of patients taking ruxolitinib (grade 3/4, 45%), and thrombocytopenia was reported in 70% (grade 3/4, 13%).14 This first JAK inhibitor therapy for myelofibrosis has been long anticipated; yet, the value of this treatment is not truly known. The treatment of adverse events and ...
Промежуточные результаты рандомизированного исследования посттрансплантационного циклофос- фана и кроличьего АТГ в качестве профилактики реакции трансплантат против хозяина у пациентов с миелопролиферативными заболеваниями и мие- лодиспластическим синдромUpdate on the randomized trial of post-transplanation cyclophosphamide and rabbit ATG for graft-versus-host disease prophylaxis in chronic myeloproliferative neoplasms and myelodysplastic syndrome
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the translocation, ETV6, leukemia gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Jul 2008 ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the translocation, ETV6, leukemia gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Jul 2008 ...
ITF2357, also known as givinostat, is a potent inhibitor of both class I and class II histone deacetylase (HDAC) as well as a potent inhibitor of hematopoietic colony formation by JAKEV617F-bearing progenitor cells from chronic myeloproliferative neoplasm
SIDE EFFECTS OF HYDROXYUREA IN CLASSIC CHRONIC MYELOPROLIFERATIVE NEOPLASMS. A RETROSPECTIVE STUDY OF 3,411 PATIENTS E Antonioli 1, P Guglielmelli 2, L Pieri 2, MC Finazzi 3, E Rumi 4, V Martinelli 5, N Vianelli 6, ML Randi 7, I Bertozzi7 , V De Stefano 8, T Za 8,M Ruggeri 9, F Rodeghiero 9, E Elli 10, E Pogliani 10, R Cacciola 11, E Cacciola 11, G Leone 8, M Baccarani6 , F Passamonti 4, G Finazzi 3, A Rambaldi 3, A Bosi2, T Barbui 3, A Vannucchi 2 1- AOU Careggi, Firenze, Italy ...
When I was around 5 months pregnant an ultrasound revealed a birth defect (duodenal atresia - a blockage between the intestines and stomach) in Tomas which also meant he had a high chance of being a Down Syndrome baby. About a month before he was born I had an amnio that showed he did indeed have DS. He was born on January 16, 2009 and had his first surgery when he was 32 hours old. After that, test result after test result rolled in. In the first month my family learned he had three holes in his heart, his liver was not working, and he had Transient Myeloproliferative disorder (a type of leukemia which resolves in the first few months of life). The second month revealed laryngomalacia (a collapsing larynx), primary and secondary aspiration, and severe reflux. He was switched to tube feedings and had his second surgery to correct the reflux that was causing him to suffocate. The TMD resolved when he was 4 months old, his liver started working when he was 5 months old, and the holes in his heart ...
When I was around 5 months pregnant an ultrasound revealed a birth defect (duodenal atresia - a blockage between the intestines and stomach) in Tomas which also meant he had a high chance of being a Down Syndrome baby. About a month before he was born I had an amnio that showed he did indeed have DS. He was born on January 16, 2009 and had his first surgery when he was 32 hours old. After that, test result after test result rolled in. In the first month my family learned he had three holes in his heart, his liver was not working, and he had Transient Myeloproliferative disorder (a type of leukemia which resolves in the first few months of life). The second month revealed laryngomalacia (a collapsing larynx), primary and secondary aspiration, and severe reflux. He was switched to tube feedings and had his second surgery to correct the reflux that was causing him to suffocate. The TMD resolved when he was 4 months old, his liver started working when he was 5 months old, and the holes in his heart ...
This presentation summarizes the findings of the Association for Molecular Pathology Chronic Myeloid Neoplasm Working Group. Chronic myeloid neoplasms (CMNs) are defined as a complex group of hematopoietic disorders, encompassing myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), the overlap entities (MDS/MPNs), and systemic mastocytosis. The goal of this group was to distill the vast amounts of literature on the mutational profiles of the CMNs into high impact information that would aid molecular pathologists in the development of next generation sequencing (NGS) myeloid panels. This work identifies 34 genes as the minimum recommended testing list and provides information on the frequency of these genes in the various CMNs as well as their prognostic and therapeutic import. In addition, the findings highlight the recurrent patterns of mutational clonal evolution in these patients, uncovering critical insight into the biology of these neoplasms.. Learning Objectives:. ...
Abdominal ultrasound may be helpful in the diagnosis of myeloproliferative neoplasm. Findings on abdominal ultrasound suggestive of myeloproliferative neoplasm include splenomegaly, abdominal fluid, and hepatic lesions. Ultrasound of the extremities can assist with diagnosis of deep vein thrombosis, which is commonly associated with high-risk polycythemia vera. ...
Another form of leukemia, transient myeloproliferative leukemia, is identified with a heterozygous C to A transversion as well. In a 2002 leukemia journal written by Taketani et al., the RUNX1 gene was screened and studied in a sample group of 46 patients with down syndrome. These patients all had hematologic malignancies, meaning they were all affected by different cancers associated with bone marrow. Out of these patients, was identified with this C to A transversion and diagnosed with transient myeloproliferative leukemia 5 days after birth. However, the newborn patient died 12 months after birth. The newborn was never screened for acute myeloid leukemia. The conclusion here is that if there is an identified C-A mutation regarding the RUNX1 gene, then AML should be screened and tested for. An amniotic fluid test should be given to pregnant women in order to determine if their children carry the mutated gene associated with acute myeloid leukemia. http://omim.org/entry/151385#0008 ...
New York, NY -- 01/12/2018 -- Idiopathic myelofibrosis is a chronic myelo-proliferative disorder and characterized by abnormal mutation of stem cells. This abnormal mutation of stem cells and excessive production of platelets result in development of fibrous tissues within the bone-marrow. This factor would ultimately negatively affect on the development of white blood cells (WBCs),…
Contents: Preface; Part I. Diagnostic Techniques: 1. Morphology Wendy N. Erber; 2. Immunocytochemistry Wendy N. Erber; 3. Flow cytometry Maryalice Stetler-Stevenson and Constance M. Yuan; 4. Cytogenetics Christine J. Harrison and Claire Schwab; 5. Molecular genetics Ken Mills; Part II. Hematological Malignancies: 6. The integrated approach to the diagnosis of hematological malignancies Mike A. Scott and Wendy N. Erber; 7. Acute lymphoblastic leukemia Elaine Coustan-Smith and Dario Campana; 8. Acute myeloid leukemia David Grimwade; 9. Mature B cell leukemias Constantine S. Tam and Michael J. Keating; 10. Mature T cell and natural killer-cell leukemias Kaaren K. Reichard and Kathryn Foucar; 11. Lymphoma Jennifer Herrick and Ahmet Dogan; 12. Plasma cell neoplasms Rafael Fonseca and Riccardo Valdez; 13. Chronic myeloid leukemia Emma J. Gudgin and Brian Huntly; 14. Myeloproliferative neoplasms Philip A. Beer and Anthony R. Green; 15. Myelodysplastic syndromes and myelodysplastic/myeloproliferative ...
PV patients may show no signs for years, but treatment is essential to manage the disease. Tune in to hear Dr. David Snyder as he shares an overview of PV and available treatments.
Primary myelofibrosis is a clonal disorder arising from the neoplastic transformation of early hematopoietic stem cells. Older terms for this disorder include agnogenic myeloid metaplasia with myelofibrosis and chronic idiopathic myelofibrosis.
Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center, discusses molecular abnormalities and their use in the diagnosis, risk stratification, and selection of treatment for myelofibrosis.. ...
Focusing on patients with polycythemia vera who were hydroxyurea-resistant/intolerant patients and ineligible for clinical trials, a phase 3b, expanded treatment protocol study demonstrated that ruxolitinib is safe and effective for this patient population. The study reported ,50% spleen reduction was achieved in 86.7% of patients, and dose adjustment/interruption due to adverse events occurred in 37.9% and study drug discontinuation in 8.7% of patients.. Leukemia & Lymphoma ...