TY - JOUR. T1 - Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib. AU - Cortes, Jorge E.. AU - Jean Khoury, H.. AU - Kantarjian, Hagop. AU - Brümmendorf, Tim H.. AU - Mauro, Michael J.. AU - Matczak, Ewa. AU - Pavlov, Dmitri. AU - Aguiar, Jean M.. AU - Fly, Kolette D.. AU - Dimitrov, Svetoslav. AU - Leip, Eric. AU - Shapiro, Mark. AU - Lipton, Jeff H.. AU - Durand, Jean Bernard. AU - Gambacorti-Passerini, Carlo. PY - 2016/6/1. Y1 - 2016/6/1. N2 - Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1/2 study of second-/third-/fourth-line bosutinib for Ph+ leukemia resistant/intolerant to prior TKIs (N=570) ...

Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Burkitt ...

Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Myelodysplastic Syndromes Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Burkitt ...

The added value of 2nd generation tyrosine kinase inhibitors (TKIs) is currently perhaps the most-discussed issue in chronic myeloid leukemia (CML) research and treatment. Therefore, with their recently published article Second-generation tyrosine kinase inhibitors improve the survival of patients with chronic myeloid leukemia in whom imatinib therapy has failed, Ibrahim et al.1 focussed on an important topic. However, in our opinion, the methodological approach used in this paper is not always appropriate.. The choice of the historical control group treated with interferon-alfa seems not to be optimal. Even before the imatinib era, progress had been made in the treatment of CML as the results of the consecutive German studies and of the French CML-study group show.2-4 We doubt that the results of the 20-year old MRC trial represent an appropriate comparator group for the results achieved by the use of 2nd generation tyrosine kinase inhibitors. Furthermore, the authors use two different ...

TY - JOUR. T1 - Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210(bcr-abl) tyrosine kinase activity. AU - Schwartz, Gretchen N.. AU - Liu, Yue Qin. AU - Tisdale, John. AU - Walshe, Kate. AU - Fowler, Daniel. AU - Gress, Ronald. AU - Bergan, Raymond C.. PY - 1998/1/1. Y1 - 1998/1/1. N2 - p210(bcr-abl)-Related tyrosine kinase activity has been shown to cause chronic myelogenous leukemia (CML), a disease of bone marrow stem cells. Having previously demonstrated that the aptameric oligonucleotide, ODN-1, could inhibit p210(bcr-abl) kinase activity, the current study sought to determine if ODN-1 could selectively inhibit the growth of CML cells relative to that of normal bone marrow. ODN-1, when introduced by electroporation into peripheral blood mononuclear cells (PBMC) from patients with CML, decreased the number of committed progenitors (CML CFU-GM) by an average of 67% ± 19% (mean ± SEM, range 28-98%). Treatment of CML PBMC with ODN-1 was also ...

TY - JOUR. T1 - Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. AU - OHare, Thomas. AU - Deininger, Michael W.N.. AU - Eide, Christopher A.. AU - Clackson, Tim. AU - Druker, Brian J.. PY - 2011/1/15. Y1 - 2011/1/15. N2 - Beginning with imatinib a decade ago, therapy based on targeted inhibition of the BCR-ABL kinase has greatly improved the prognosis for chronic myeloid leukemia (CML) patients. The recognition that some patients experience relapse due to resistance-conferring point mutations within BCR-ABL sparked the development of the second-generation ABL kinase inhibitors nilotinib and dasatinib. Collectively, these drugs target most resistant BCR-ABL mutants, with the exception of BCR-ABLT315I. A third wave of advances is now cresting in the form of ABL kinase inhibitors whose target profile encompasses BCR-ABLT315I. The leading third-generation clinical candidate for treatment-refractory CML, including patients with the T315I ...

Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow - the spongy tissue inside bones where blood cells are made. CML causes an increased number of white blood cells in the blood.. The term chronic in chronic myelogenous leukemia indicates that this cancer tends to progress more slowly than acute forms of leukemia. The term myelogenous (my-uh-LOHJ-uh-nus) in chronic myelogenous leukemia refers to the type of cells affected by this cancer.. Chronic myelogenous leukemia can also be called chronic myeloid leukemia and chronic granulocytic leukemia. It typically affects older adults and rarely occurs in children, though it can occur at any age.. Advances in treatment have contributed to a greatly improved prognosis for people with chronic myelogenous leukemia. Most people will achieve remission and live for many years after diagnosis. ...

A phase of chronic myelogenous leukemia in which the disease is progressing. In this phase, 10% to 19% of the cells in the blood and bone marrow are blast cells (immature blood cells).

TY - JOUR. T1 - Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia. AU - Quintás-Cardama, Alfonso. AU - Cortes, Jorge. PY - 2008/7/15. Y1 - 2008/7/15. N2 - Despite the efficacy of imatinib therapy in chronic myelogenous leukemia, the development of resistance continues to challenge the treatment of this disease. Mutations within the kinase domain of BCR-ABL1 constitute the most frequent mechanism of resistance in patients with chronic myelogenous leukemia treated with imatinib or the second generation tyrosine kinase inhibitors nilotinib and dasatinib. Of particular concern is the substitution of the threonine residue at the highly conserved gatekeeper residue 315 with a bulkier hydrophobic isoleucine amino acid. This mutation causes steric hindrance precluding the access ATP-competitive inhibitors to the ATP-binding pocket. To expedite the identification of strategies to override the resistance imposed by the T3151 mutation, several strategies have been pursued, ...

RATIONALE: Vaccines made from gene-modified cancer cells may help the body build an effective immune response to kill cancer cells. Imatinib mesylate ma

TY - JOUR. T1 - Tyrosine kinase inhibitor therapy can cure chronic myeloid leukemia without hitting leukemic stem cells. AU - Lenaerts, Tom. AU - Pacheco, Jorge M.. AU - Traulsen, Arne. AU - Dingli, David M. PY - 2010/6. Y1 - 2010/6. N2 - Background: Tyrosine kinase inhibitors, such as imatinib, are not considered curative for chronic myeloid leukemia - regardless of the significant reduction of disease burden during treatment - since they do not affect the leukemic stem cells. However, the stochastic nature of hematopoiesis and recent clinical observations suggest that this view must be revisited. Design and Methods: We studied the natural history of a large cohort of virtual patients with chronic myeloid leukemia under tyrosine kinase inhibitor therapy using a computational model of hematopoiesis and chronic myeloid leukemia that takes into account stochastic dynamics within the hematopoietic stem and early progenitor cell pool. Results: We found that in the overwhelming majority of patients ...

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing ...

Title: Interferon alpha for Treatment of Chronic Myeloid Leukemia. VOLUME: 12 ISSUE: 3. Author(s):Bengt Simonsson, Henrik Hjorth-Hansen, Ole Weis Bjerrum and Kimmo Porkka. Affiliation:Department of Hematology 50C, Uppsala University Hospital, Uppsala, 75185 Sweden.. Keywords:Interferon-alpha, chronic myeloid leukemia, imatinib, combination therapy, chronic myeloid leukemia stem cells, BCR, BCR-ABL1, CML cell, fluorescent in situ hybridization, allogeneic stem cell transplantation, allogeneic SCT, poietic stern cells, leukemic effect in CML, psychosis, autoimmune disorders, thyreoiditis. Abstract: Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. > 2 log tumor mass reduction). IFN-α was then recommended as first line medical treatment until ...

We have followed one patient with Philadelphia (Ph)-negative chronic myelogenous leukemia and identified an additional four patients from the literature who showed the rearrangement in the breakpoint cluster region (bcr) on chromosome 22 characteristic of Ph-positive chronic myelogenous leukemia. The clinical course of these five patients was similar to that of Ph-positive patients, with easily controlled leukocyte counts, a prolonged benign phase, and prolonged survival. Furthermore, we have shown, for the first time, that bcr rearrangement in Ph-negative chronic myelogenous leukemia can result in expression of the aberrant 210-kilodalton bcr-abl fusion protein, which has been strongly implicated in Ph-positive leukemogenesis. Research data pertaining to possible cytogenetic mechanisms leading to production of p210bcr-abl in the absence of the Ph chromosome are reviewed. Molecular analysis provides an important tool for classifying and predicting prognosis of some patients with Ph-negative ...

TY - JOUR. T1 - Prominent hematogone hyperplasia in BCR-ABL1-positive chronic myelogenous leukemia. T2 - Mimicking recurrent B-lymphoid blast crisis. AU - Horna, Pedro. AU - Pantazopoulos, Panagiotis. AU - Lancet, Jeffrey E.. AU - Moscinski, Lynn C.. AU - Zhang, Ling. PY - 2014/8. Y1 - 2014/8. UR - http://www.scopus.com/inward/record.url?scp=84904886239&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84904886239&partnerID=8YFLogxK. U2 - 10.3109/10428194.2013.869330. DO - 10.3109/10428194.2013.869330. M3 - Letter. C2 - 24304373. AN - SCOPUS:84904886239. VL - 55. SP - 1952. EP - 1954. JO - Leukemia and Lymphoma. JF - Leukemia and Lymphoma. SN - 1042-8194. IS - 8. ER - ...

The BCR-ABL1 oncoprotein is found in a subset of patients with ALL carrying the Philadelphia chromosome. This translocation is the most common cytogenetic abnormality in adults, with ALL occurring in 25% of patients (33). BCR-ABL1 defines a high-risk group and, as such, patients receive intensive chemotherapy in combination with ABL TKIs and are considered for hematopoietic stem cell transplantation (HSCT). Despite the great success with combination of high-dose ABL TKIs and intensive chemotherapy, there are still drawbacks that need to be addressed. Above all, 40% of patients, even with HSCT, have relapse of the disease. Furthermore, it is not clear whether responsive patients without HSCT cannot have relapse of the disease, as there is evidence that BCR-ABL1-positive leukemia stem cells remain present in the patients bone marrow even after years of therapy. Therefore, it is necessary to define targets in BCR-ABL1-positive leukemia stem cells that may be candidates for new treatment ...

Read about the report that tyrosine kinase inhibitors therapy is relatively safe for kidney function in chronic myeloid leukemia patients.

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The significance of molecular response depth is not well defined in patients with chronic phase chronic myeloid leukemia (CP-CML) under imatinib treatment. We retrospectively evaluated clinical records of 178 patients with CP-CML. Eighty-eight patients achieved complete molecular response during long term follow-up. Our results implicate that deeper molecular response is associated with improvement in disease outcome and a slight prolongation in progression-free survival. ...

Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TIC). This discovery has led to the cancer stem cell hierarchy concept, which holds that tumors are organized as a hierarchy of malignant tissues sustained by such TIC. However, this concept remains controversial. In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia (Ph) chromosome-positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1 fusion gene, is most commonly associated with chronic myelogenous leukemia (CML) and precursor B cell acute lymphoblastic leukemia (B-ALL). Examination of the pathophysiology of these diseases has provided interesting insights into not only the hierarchy of leukemia stem cells but also their clonal evolution. Both shared and unique regulatory mechanisms affecting normal and CML stem ...

Tyrosine kinase inhibitors (TKIs) induce molecular remission in the majority of patients with chronic myelogenous leukemia (CML), but the persistence of CML stem cells hinders cure and necessitates indefinite TKI therapy. We report that CML stem cells upregulate the expression of pleiotrophin (PTN) and require cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL+ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. Hematopoietic cell-specific deletion of PTN suppressed CML development in BCR/ABL+ mice, suggesting that cell-autonomous PTN signaling was necessary for CML disease evolution. Mechanistically, PTN promoted CML stem cell survival and TKI resistance via induction of Jun and the unfolded protein response. Human CML cells were also dependent on cell-autonomous PTN signaling, and anti-PTN antibody suppressed human CML colony formation and CML repopulation in vivo. Our results suggest that targeted inhibition of PTN ...

The FDA has approved bosutinib (Bosulif) to treat chronic myelogenous leukemia (CML). The drug is intended for patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who are resistant to or who cannot tolerate other therapies, including imatinib (Gleevec).. The safety and effectiveness of Bosulif was evaluated in a single clinical trial that enrolled 546 adult patients with chronic, accelerated, or blast phase CML. All patients had disease that progressed after treatment with imatinib or imatinib followed by dasatinib (Sprycel) and/or nilotinib (Tasigna), or who could not tolerate the side effects of prior therapy.. Results showed 34% of patients with chronic phase CML who had been previously treated with imatinib achieved a major cytogenetic response after 24 weeks. Of the patients who achieved a major cytogenetic response at any time, 52.8% had their response last at least 18 months. Among patients previously treated with imatinib followed by dasatinib and/or ...

Clinical trial for Chronic myeloid leukemia , Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients

The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...

The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...

The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...

The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative. Here, we show that CP-CML, BC-CML, and AML stem cells upregulate MHCII in alloSCT recipients. Using gene-deficient leukemias, we determined that BC-CML and AML MHC upregulation required IFN-γ stimulation, whereas CP-CML MHC upregulation was independent of both the IFN-γ receptor (IFN-γR) and the IFN-γ/γ receptor IFNAR1. Importantly, IFN-γR-deficient BC-CML and AML were completely resistant ...

Tyrosine kinase inhibitors (TKIs) induce molecular remission in the majority of patients with chronic myelogenous leukemia (CML), but persistence of CML stem cells hinders cure and necessitates indefinite TKI therapy. We report that CML stem cells upregulate expression of pleiotrophin (PTN) and require cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL+ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. Hematopoietic cell-specific deletion of PTN suppressed CML development in BCR/ABL+ mice, suggesting that cell-autonomous PTN signaling was necessary for CML disease evolution. Mechanistically, PTN promoted CML stem cell survival and TKI resistance via induction of Jun and the unfolded protein response. Human CML cells were also dependent on cell-autonomous PTN signaling and anti-PTN antibody suppressed human CML colony formation and CML repopulation in vivo. Our results suggest that targeted inhibition of PTN has ...

In this retrospective analysis, fourteen/18 (78%) evaluable patients were found challenged with higher doses of IM (600-800 mg/day), with one return to CP and one transient CCyR after IM combined with chemotherapy, and 12 failures. Six patients (1 CP, 5 BC) were treated with dasatinib, and no difference in survival was seen between dasatinib-treated and non-treated patients (p=0.15). None of the patients received nilotinib. Additionally, 3 patients underwent allogeneic stem cell transplantation with 2 remaining alive at 1 and 14 months follow-up. Finally, at latest follow-up, overall survival since IM initiation (Figure 1B), however longer for CP (42.5 Mo.) was not statistically different than that for AP+BC (17.5 Mo., p=0.08) patients.. The onset of BCR-ABLT315I mutations during the treatment of CML with TKIs remains challenging, because this mutation is the most frequently identified in IM-treated patients6, and none of the TKIs clinically available to date4,5,6 retain any activity in vitro. ...

Tasigna (nilotinib) is approved in more than 122 countries for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) in adult patients resistant or intolerant to at least one prior therapy, including Glivec (imatinib), and in more than 110 countries for the treatment of adult patients with newly diagnosed Ph+ CML in chronic phase. Tasigna is approved in the European Union (EU) for the treatment of Ph+ CML in the chronic phase in pediatric patients with resistance or intolerance to prior therapy including Glivec and for the treatment of pediatric patients with newly diagnosed Ph+ CML in the chronic phase.. IMPORTANT SAFETY INFORMATION for TASIGNA® (nilotinib) Capsules Use with caution in patients with uncontrolled or significant cardiac disease and in patients who have or may develop prolongation of QTc. Low levels of potassium or magnesium must be corrected prior to Tasigna administration. Monitor closely for an effect on ...

The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5′ part of the BCR gene on chromosome 22 to the 3′ part of the ABL gene on chromosome 9. Since the majority of CML cases are currently treated with Imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. The T315I mutation within the abl-gene is the most frequent one associated with resistance to tyrosine kinase inhibitors. This study evaluated a Ph chromosome positive CML case resistant to imatinib mesylate. A dic(17;18), loss of TP53 gene, co-expression of b2a2 and b3a2 fusions transcript and a T315I mutation were found. We reported here a novel case of a Ph chromosome positive CML with a secondary abnormality [dic(17;18)], resulting to Glivec resistance but good response to nilotinib. The dic(17;18) might be a marker for poor prognosis

53 NCCN Guidelines for Patients ® : Chronic Myeloid Leukemia, 2018 Acronyms Acronyms ALL acute lymphoblastic leukemia AML acute myeloid leukemia CAM complementary and alternative medicine CBC complete blood count CCyR complete cytogenetic response CBC complete blood count CML chronic myeloid leukemia CMR complete molecular response DLI donor lymphocyte infusion DNA deoxyribonucleic acid EMR early molecular response FDA Food and Drug Administration FISH fluorescence in situ hybridization GVL graft-versus-leukemia HCT hematopoietic cell transplant HLA human leukocyte antigen IS International Scale NCCN National Comprehensive Cancer Network MMR major molecular response MPN myeloproliferative neoplasm QPCR quantitative reverse transcriptase-polymerase chain reaction TKI tyrosine kinase inhibitor ...

For hematologic toxicity, treatment should be withheld for an absolute neutrophil count , 1,000 × 106/L or platelets , 50,000 × 106/L until levels increase above these thresholds. Treatment can be resumed at the same dose if recovery occurs within 2 weeks and at a dose reduced by 100 mg if recovery takes , 2 weeks. If cytopenia recurs, the dose should be reduced by an additional 100 mg when restarting treatment after recovery.. Concomitant use of bosutinib with strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin), moderate CYP3A inhibitors (eg, erythromycin, fluconazole, diltiazem), or strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin) should be avoided. Short-acting antacids or H2 blockers should be used as an alternative to proton pump inhibitors.. Safety Profile IN THE TOTAL population of the phase III trial, the most common adverse events of any grade in the bosutinib group were diarrhea (70% vs 34% in imatinib group), nausea (35% vs 38%), thrombocytopenia ...

abstract = In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1-3 courses of intensive chemotherapy. Those who became Ph-negative after IFN+HU or after 1-3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN+HU reduced the percentage of Ph-positive metaphases in 56{\%} of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88{\%} had a Ph ...

article{801ae827-4c64-4154-8fc7-42929426f3d8, abstract = {In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1-3 courses of intensive chemotherapy. Those who became Ph-negative after IFN+HU or after 1-3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN+HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive ...

There are several treatments used for blast phase chronic myelogenous leukemia. Learn about treatments that may be offered to treat blast phase CML.

The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML.. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML.. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML.. CITATION Mol Cancer. 2009 Sep 1;8:69. ...

Semantic Scholar extracted view of Dasatinib-induced pulmonary hypertension in chronic myelogenous leukaemia. by Seongseok Yun et al.

K-562 Cell Slide (Human (53yrs, Female) bone marrow, chronic myelogenous leukemia (CML)) (5 slides/pk) Slide for ICC HCLS-17004 K-562 Cell Slide (Human (53yrs, Female) bone marrow, chronic myelogenous leukemia (CML)) (5 slides/pk) Slide for ICC HCLS-17004

Chronic myelogenous leukemia treatments include tyrosine kinase inhibitors, high-dose therapy with allogeneic transplantation, and other medications. Get detailed information about chronic myelogenous leukemia (CML) treatment options in this summary for clinicians.

The US Food and Drug Administration (FDA) has approved Bosulif (bosutinib) to treat adults with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).Indications: Bosulif is a kinase inhibitor indicated for the treatment of adult patients with newly-diagnosed chronic phase Ph+ CML.Dosage and administration: 400 mg orally once daily with food.

Chronic myeloid leukaemia. Light micrograph of blood cells from bone marrow in a case of chronic myeloid leukaemia. Leukaemia is a cancer where certain blood cells form in excess. There are several chronic forms, classified according to the type of cell affected. Chronic myeloid leukaemia is a cancer affecting the myeloid tissue (bone marrow), specifically the white blood cell precursors (myeloblasts) that form a type of white blood cell known as granulocytes. The pink cells are precursor or white blood cells. The pale orange ones are red bloods cells. Magnification: x1000 when printed at 10 centimetres across. - Stock Image C015/1835

Hematology: Chronic myelogenous leukemia (cml) | Stem cell transplant. Treatment in Ulm, Germany ✈ Find the best medical programs at BookingHealth - ✔Compare the prices ✔Online booking.

Imatinib became the front-line treatment for patients with chronic-phase chronic myelogenous leukemia (CP-CML) based on results from the International Randomized Study of Interferon and STI571 (IRIS), which compared imatinib versus interferon-α combined with low-dose cytarabine.1 According to the 5-year follow-up of the IRIS trial, imatinib used as initial therapy produced a cumulative complete cytogenetic response (CCyR) rate of 87%.1,2 The 8-year follow-up, presented in abstract form only, revealed estimated overall and event-free survivals of 85% and 81%, respectively.3 Patients receiving imatinib have also reported improved health-related quality of life.4 However, approximately 30% of the patients develop resistance and/or intolerance to imatinib.5 The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib have increased potency compared with imatinib.6,7 They were approved initially for patients in whom imatinib had failed, and subsequently for front-line treatment of ...

TY - JOUR. T1 - Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice. T2 - Identification of risk factors and the role of prophylaxis. AU - Caocci, Giovanni. AU - Mulas, Olga. AU - Annunziata, Mario. AU - Luciano, Luigiana. AU - Bonifacio, Massimiliano. AU - Orlandi, Ester Maria. AU - Pregno, Patrizia. AU - Galimberti, Sara. AU - Russo Rossi, Antonella. AU - Abruzzese, Elisabetta. AU - Iurlo, Alessandra. AU - Martino, Bruno. AU - Sgherza, Nicola. AU - Binotto, Gianni. AU - Castagnetti, Fausto. AU - Gozzini, Antonella. AU - Fozza, Claudio. AU - Bocchia, Monica. AU - Sicuranza, Anna. AU - Stagno, Fabio. AU - Efficace, Fabio. AU - Usala, Emilio. AU - De Gregorio, Fiorenza. AU - Scaffidi, Luigi. AU - Elena, Chiara. AU - Pirillo, Francesca. AU - Baratè, Claudia. AU - Trawinska, Malgorzata Monika. AU - Cattaneo, Daniele. AU - Labate, Claudia. AU - Gugliotta, Gabriele. AU - Molica, Matteo. AU - Specchia, ...

Detection of Human IRAK2 by Western Blot. Western blot shows lysates of Jurkat human acute T cell leukemia cell line, Raji human Burkitts lymphoma cell line, K562 human chronic myelogenous leukemia cell line, and HeLa human cervical epithelial carcinoma cell line. PVDF Membrane was probed with 0.5 µg/mL of Human IRAK2 Monoclonal Antibody (Catalog # MAB6690) followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF007). A specific band was detected for IRAK2 at approximately 65 kDa (as indicated). This experiment was conducted under reducing conditions and using Immunoblot Buffer Group 1 ...

The (9;22) translocation which produces the Philadelphia (Ph1) chromosome activates the abl oncogene from chromosome 9 by recombination with the bcr gene from chromosome 22. This fusion gene is transcribed into a new 8.5-kilobase chimeric mRNA which is translated into a novel Mr 210,000 fusion protein which has a protein tyrosine kinase activity that is greatly increased in comparison to the activity of the normal abl protein. Studies from this laboratory and others have shown that virtually all patients with chronic myelogenous leukemia have this new bcr/abl fusion gene. In contrast to these findings in chronic myelogenous leukemia, a small number of patients with Ph1(+) acute lymphoblastic leukemia (ALL) have been studied and were found to lack the bcr/abl fusion gene [bcr(-)], but to have a new activation of abl, by recombination with an as yet undetermined region on chromosome 22. In this study, nine adults with Ph1(+)-ALL have been examined for evidence of a bcr/abl fusion gene. Of the nine ...

TY - JOUR. T1 - Immunophenotypic and genotypic characteristics of chronic myelogenous leukemia in blast crisis. AU - Yen, C. C.. AU - Liu, J. H.. AU - Wang, W. S.. AU - Fan, F. S.. AU - Chiou, T. J.. AU - Tai, C. J.. AU - Yang, M. H.. AU - Chao, T. C.. AU - Hsiao, L. T.. AU - Chen, P. M.. PY - 2000. Y1 - 2000. N2 - Background. Chronic myelogenous leukemia (CML) may transform into blast crisis (BC) if not properly treated. Among patients with transformation, 20% to 30% will develop BC with lymphoid-associated antigens (Ly-BC), and the remaining cases with myeloid-associated antigens (My-BC) or with both (Mix-BC). In this study, we investigated the lineage of blast cells in CML-BC using immunophenotypic and genetic analyses and analyzed the prognostic significance of genotypic change in CML-BC. Methods. Twenty-one patients with CML-BC diagnosed at the Taipei Veterans General Hospital from 1982 to 1992 were included. Immunophenotyping was done by using the avidin-biotin immunoperoxidase technique. ...

BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial ...

TY - JOUR. T1 - Blastic Mantle Cell Lymphoma Developing Concurrently in a Patient with Chronic Myelogenous Leukemia and a Review of the Literature. AU - Rodler, Eve. AU - Welborn, Jeanna L. AU - Hatcher, Sandra. AU - Unger, Katherine. AU - Larkin, Edward. AU - Gumerlock, Paul H.. AU - Wun, Theodore. AU - Richman, Carol M. PY - 2004/4. Y1 - 2004/4. N2 - Non-Hodgkins lymphoma (NHL) occurring as a synchronous malignancy with chronic myelogenous leukemia (CML) is rare. To our knowledge, this is the first case reported of a patient who developed mantle cell lymphoma (MCL) after therapy with imatinib mesylate for CML. After a 3-year history of CML, the patient developed a lymphocytosis associated with diarrhea, anorexia, and weight loss. Imaging studies revealed abdominal adenopathy and extensive lymphomatous infiltration of the liver, stomach, pancreas, and kidneys. Flow cytometric and cytogenetic studies were consistent with MCL. Fluorescence in situ hybridization (FISH) of the bone marrow revealed ...

Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients / Alti kronik miyeloid losemi olgusunda farkli kirik noktali varyant Philadelphia translokasyonlari.

The Philadelphia chromosome (Ph1) is a translocation between chromosomes 9 and 22 that is found in chronic myelogenous leukemia (CML) and a subset of acute lymphocytic leukemia patients (ALL). In CML, this results in the expression of a chimeric 8.5-kilobase BCR-ABL transcript that encodes the P210BCR-ABL tyrosine kinase. The Ph1 chromosome in ALL expresses a distinct ABL-derived 7-kilobase messenger RNA that encodes the P185ALL-ABL protein. Since the expression of different oncogene products may play a role in the distinctive presentation of Ph1-positive ALL versus CML, it is necessary to understand the molecular basis for the expression of P185ALL-ABL. Both P210BCR-ABL and P185ALL-ABL are recognized by an antiserum directed to BCR determinants in the amino-terminal region of both proteins. Antisera to BCR determinants proximal to the BCR-ABL junction in CML immunoprecipitated P210BCR-ABL but not P185ALL-ABL. Nucleotide sequence analysis of complementary DNA clones made from RNA from the ...

Comment: Management of De Novo Chronic Myelogenous Leukemia and Imatinib-Induced Acute Rhabdomyolysis With the Second-Generation Tyrosine Kinase Inhibitor ...

Celecoxib is a selective COX-2 inhibitor and its anti-tumor effect has been reported in various cancers [7-9]. In this paper, we demonstrated that the anti-tumor activities of celecoxib included cell cycle arrest, necrosis, apoptosis and autophagy suppression in KBM5 and KBM5-T315I cells. KBM5-T315I cell is a mutation line of KBM5 with a threonine to isoleucine mutation at position 315 in the Abl fragment of the Bcr-Abl kinase domain. This leads to an alteration of the enzymes active site and makes these cells resistant to the first and second generation of TKI [35]. Results showed that celecoxib caused cytotoxic effect in the two CML cell lines which was dose and time-dependent. When extending the celecoxib incubation time, the inhibition effect was stronger in KBM5-T315I cells than in KBM5 cells (Fig. 1), indicating that celecoxib might be used as a new therapeutic agents in imatinib-resistant CML. In accordance with other reports [19, 21], our findings also confirmed that the anti-tumor ...

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 ...

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.

TY - JOUR. T1 - DETECTION OF REARRANGEMENT WITHIN THE BREAKPOINT CLUSTER REGION OF CHROMOSOME 22 IN THE DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA. AU - HUTCHINS, C.. AU - CASEY, G.. AU - White, Deborah. AU - MOORE, S.. AU - RUDZKI, Z.. AU - KIMBER, R.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - Chronic myeloid leukemia (CML) is characterised by the presence of a Philadelphia (Ph) chromosome in approximately 95% of patients. Molecular analysis has shown that the Ph chromosome translocation breakpoints are clustered within 5.8kb on chromosome 22 (breakpoint cluster region or bcr). This has facilitated the diagnosis of CML by nucleic acid hybridisation using probes specific for the bcr to detect DNA rearrangement in this region. Forty patients diagnosed with CML, including four with variant Ph chromosome translocations and three with normal karyotypes were analysed for rearrangement within the bcr. All except one patient with Ph negative CML had rearrangement within the bcr. In contrast, none of the patients ...

This study will evaluate MK0457 in combination with Dasatinib in patients with Chronic Myelogenous Leukemia and Philadelphia Chromosome-Positive Acute L

Targeting Mitochondrial Oxidative Phosphorylation Eradicates Therapy-Resistant Chronic Myeloid Leukemia Stem Cells Scientists performed metabolic analyses on both stem cell-enriched and differentiated cells derived from individuals with chronic myeloid leukemia (CML), and they compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, they demonstrated that primitive CML cells rely on upregulated oxidative metabolism for their survival. [Nat Med] Abstract Induction of Cancer Cell Stemness by Depletion of Macrohistone H2A1 in Hepatocellular Carcinoma Using hepatocellular carcinomas cell lines researchers found that shRNA-mediated macroH2A1 knock-down induces acquisition of cancer stem cells-like features, including the growth of significantly larger and less-differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to ...

TY - JOUR. T1 - Long-term data from a phase 3 study of radotinib versus imatinib in patients with newly diagnosed, chronic myeloid leukaemia in the chronic phase (RERISE). AU - Do, Young Rok. AU - Kwak, Jae Yong. AU - Kim, Jeong A.. AU - Kim, Hyeoung Joon. AU - Chung, Joo Seop. AU - Shin, Ho Jin. AU - Kim, Sung Hyun. AU - Bunworasate, Udomsak. AU - Choi, Chul Won. AU - Zang, Dae Young. AU - Oh, Suk Joong. AU - Jootar, Saengsuree. AU - Reksodiputro, Ary Harryanto. AU - Lee, Won Sik. AU - Mun, Yeung Chul. AU - Kong, Jee Hyun. AU - Caguioa, Priscilla B.. AU - Kim, Hawk. AU - Park, Jinny. AU - Kim, Dong Wook. PY - 2020/1/1. Y1 - 2020/1/1. N2 - In the phase 3 study RERISE, patients with newly diagnosed chronic myeloid leukaemia in chronic phase demonstrated significantly faster and higher rates of major molecular response (MMR) with twice-daily radotinib 300 mg (n = 79) or 400 mg (n = 81) than with once-daily imatinib 400 mg (n = 81) after 12 months. With ≥48 months follow-up, MMR was higher with ...

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the ...

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the ...

Targeted drugs are the initial treatment for most people diagnosed with chronic myelogenous leukemia. If the disease doesnt respond or becomes resistant to the first targeted drug, doctors may consider other targeted drugs, such as omacetaxine (Synribo), or other treatments. Side effects of these targeted drugs include swelling or puffiness of the skin, nausea, muscle cramps, rash, fatigue, diarrhea, and skin rashes.. Doctors havent determined a safe point at which people with chronic myelogenous leukemia can stop taking targeted drugs. For this reason, most people continue to take targeted drugs even when blood tests reveal a remission of chronic myelogenous leukemia.. Blood stem cell transplant. A blood stem cell transplant, also called a bone marrow transplant, offers the only chance for a definitive cure for chronic myelogenous leukemia. However, its usually reserved for people who havent been helped by other treatments because blood stem cell transplants have risks and carry a high rate ...

Thromboembolic events are common cause of death in patients with myeloproliferative disorders (MPD) especially those with cardiac involvement . In previous studies, cardiac involvement, including coronary arterial thrombosis, myocardial infarction, pulmonary hypertension (PHT), asymptomatic pericardial effusion, cardiac tamponade, intractable cardiac failure due to intraventricular thrombosis, and stenosis of aortic, mitral valves, even requiring surgical treatment had been reported in MPD This cohort study was carried out in three Iraqi teaching hospitals for Medicine including Al-Kadhimyya Teachginmg Hospital , Al-Yarmook Teaching Hospital (including National haematology Centre) and Merjan Teaching hospital in Babylon. The study groups were 26 patients (mean age female and male) with MPD and 30 age-matched healthy controls. MPD group included sixteen cases chronic phase chronic myelogenous leukemia (CML), two idiopathic myelofibrosis (MF) , seven polcythemia vera and one essential ...

Williams LA, Ault P, Garcia-Gonzalez A, et al. Relationship of patient-reported symptoms to daily functioning in chronic myeloid leukemia [abstract]. American Society of Hematology 54th Annual Meeting and Exposition, Atlanta GA, Dec 8-11, 2012. Blood 118(21): 2012; 4260.. Williams LA, Jacobsen PB, Sailors MH, et al. Symptoms in chronic myeloid leukemia survivors on tyrosine kinase inhibitor therapy at two cancer centers [abstract]. Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) 2012 International Symposium on Supportive Care in Cancer, New York NY, Jun 28-30, 2012. Support Care Cancer 20(Suppl 1): S240, 2012; 1003.. Garcia-Gonzalez A, Ault P, Williams LA, Williams JL, Cleeland CS, Cortes JE. Interactive voice response system compliance in chronic myeloid leukemia population [abstract]. American Society of Clinical Oncology 48th Annual Meeting, Chicago IL, Jun 1-5, 2012; e19589.. Williams LA, Ault PS, Garcia-Gonzalez A, et al. ...

Belson M, Kingsley B, Holmes A. Risk factors for acute leukemia in children: a review.Environ Health Perspect. 2007;115(1):138-145.. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.Sci Transl Med. 2013;5(177):177ra38.. Campana D, Pui C-H. Childhood Leukemia. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds.Abeloffs Clinical Oncology. 5th ed. Elsevier Saunders; 2013:1849-1872.e11.. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075-2088.. Diller L. Clinical practice. Adult primary care after childhood acute lymphoblastic leukemia.N Engl J Med. 2011;365(15):1417-1424.. Faderl S, OBrien S, Pui CH, et al. Adult acute lymphoblastic leukemia: concepts and strategies.Cancer. 2010;116(5):1165-1176.. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T ...

We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse of CML following transplant (5-year Kaplan-Meier estimate of relapse, 20%; 95% confidence interval [CI], 11 to 30%). One of 12 patients transplanted in second stable phase following blast crisis also relapsed. Fifteen related-donor transplant recipients relapsed within 5 years of transplant; however, seven relapsed between 5 and 9 years after transplant. Factors independently associated with an increased risk of posttransplant relapse for related-donor recipients included prolonged interval between diagnosis and transplant (relative risk, [RR], 3.81; P = .009) and bone marrow basophilia (RR, 5.62; P = .01). Related-donor recipients with posttransplant chronic graft-versus-host ...

p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...

The t(9;22)(q34;q11) chromosomal translocation is the most frequent cytogenetic abnormality found in human leukemias where it can be detected in ∼95% of patients with chronic myelogenous leukemia (CML) and in 30% to 40% of pre-B and acute lymphoblastic leukemia (1-3). This translocation results in the fusion of the BCR and ABL genes, leading to the expression of a BCR-ABL fusion protein with constitutively active ABL tyrosine kinase activity (1, 4). BCR-ABL-induced signaling is known to activate Ras-dependent signaling, phosphatidylinositol-3-kinase/Akt, and the Jak/STAT pathway (5). Additionally, BCR-ABL activates the transcription factor nuclear factor-κB (NF-κB) at least partly in a manner dependent on Ras (6). Suppression of NF-κB activation by expression of the so-called superrepressor form of IκBα blocked BCR-ABL-dependent xenograft tumor formation (6). Others (7) have also observed that NF-κB is activated by BCR-ABL in manner dependent on Ras. Furthermore, that study reported ...

Novartis AGs Tasigna, for children one year of age or older with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase, or Ph+ CML-CP. The drug is already approved to treat adults and children with Ph+ CML-CP resistant or intolerant to prior tyrosine kinase inhibitor therapy and prior therapy.. * Orthofix International NVs G-Beam fusion beaming system, for Charcot foot. The company received 510(k) clearance.. * Sun Pharmaceutical Industries Ltd.s Ilumya, for moderate to severe plaque psoriasis.. * Seattle Genetics Inc.s Adcetris-chemotherapy combination, for adults with previously untreated stage 3 or 4 classical Hodgkin lymphoma. The drug is already approved to treat three other types of lymphoma as well as certain patients with mycosis fungoides. Seattle Genetics is developing Adcetris with Takeda Pharmaceutical Co. Ltd.. * Restoration Robotics Inc.s Artas hair transplantation system, for pattern baldness. The company received 510(k) ...

We report a 34 year old man who developed bilateral ptosis and predominantly respiratory, truncal and bulbar weakness, and a high titer of anti acetylcholine receptor antibodies along with a diagnosis of Philadelphia chromosome positive Chronic Myeloid Leukemia (CML). The temporal relationship suggests a possible association.. ...

allogeneic stem cell transplant is the only potential cure for chronic myelogenous leukemia (cml). the procedure is usually done if youre young and dont have any medical issues besides cml.