Mutations leukemia myelomonocytic chronic. Medical search. Frequent questions

In fact, ASXL1 mutations are the most common mutations in CMML, seen in around 40% of cases. (medscape.com)
We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1 MT in chronic myelomonocytic leukemia (CMML). (nature.com)
Within myeloid neoplasms, chronic myelomonocytic leukemia (CMML) represents an attractive disease model since it is characterized by both myelodysplastic and myeloproliferative features, while retaining a relatively simple clonal composition 3 . (nature.com)
CMML shares the typical repertoire of genetic driver lesions with other myeloid neoplasms and is particularly enriched in truncating mutations involving ASXL1 (prevalence ~40%) 3 . (nature.com)
Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. (wikipedia.org)
The current study attempts to demonstrate the existence of double minute chromosomes via FLT3 gene amplification in a patient diagnosed with chronic myelomonocytic leukemia (CMML). (hindawi.com)
Here, to our best knowledge, we present the first case of amplification encompassing the FLT3 gene acting as dmin in a patient with chronic myelomonocytic leukemia (CMML). (hindawi.com)
In the presence of RAS-pathway mutations, GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML).6,7,8 Therefore, lenzilumab's ability to prevent GM-CSF binding to its receptor may inhibit the hyperproliferation in these conditions. (biospace.com)
Translocations and other types of mutations involving the RUNX1 gene have been associated with different types of leukemia and related blood disorders, including acute lymphoblastic leukemia (ALL), chronic myelomonocytic leukemia (CMML), familial platelet disorder with predisposition to acute myeloid leukemia, and myelodysplastic syndromes (MDS). (medlineplus.gov)
TET2-knockout mice predominantly develop chronic myelomonocytic leukemia (CMML), but they can also develop other myeloproliferative as well as lymphoproliferative diseases, reflecting the prevalence of TET2 mutations in these varied hematologic malignancies. (aacrjournals.org)
Frameshift and nonsense mutations occur frequently in CMML, acute myeloid leukemia ( 3 ), and myeloproliferative neoplasm (MPN) cases ( 4 ). (aacrjournals.org)
Chronic Myelomonocytic Leukemia (CMML) is a type of leukemia that is characterized by high numbers of white blood cells, called "monocytes", in the blood and bone marrow. (menarini.com)
Several prognostic scoring systems have been proposed for chronic myelomonocytic leukemia (CMML), a disease in which some gene mutations-including ASXL1-have been associated with poor prognosis in univariable analyses. (jax.org)
It is under development for the treatment of clonal cytopenia of undetermined significance (CCUS), hematologic malignancies including untreated or relapsed and refractory AML (in the EU), and myelodysplastic syndrome (MDS), relapsed/ refractory multiple myeloma, chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasm solid tumors, hepatic impairment. (pharmaceutical-technology.com)
Chronic myelomonocytic leukemia (CMML) is a rare form of blood cancer that forms in the cells of the bone marrow before invading the blood cells. (patientworthy.com)
According to the 2017 World Health Organization (WHO) classification, this category currently includes four adult subtypes: chronic myelomonocytic leukemia (CMML), BCR-ABL1 -negative atypical chronic myeloid leukemia (aCML), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), MDS/MPN-unclassifiable (MDS/MPN-U), and one pediatric entity: juvenile myelomonocytic leukemia (JMML) [ 1 ] . (encyclopedia.pub)
Unfortunately, at 54 years of age, she developed a secondary cancer of therapy-related (t-) chronic myelomonocytic leukemia (t-CMML). (frontiersin.org)
She developed ovarian cancer, and then the altered FA pathway plus exposure to cytotoxic drugs promoted the emergence of acquired somatic mutations and the NUP98-HOXC11 fusion, all of which contributed to the development of secondary t-CMML. (frontiersin.org)
In the presence of RAS -pathway mutations, GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML). (stocktitan.net)
NPM1 gene mutations are rarely detected in patients with non-acute MNs, such as myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML)," wrote the authors, led by Chen Wang, MD, of the Department of Internal Medicine in the Morsani College of Medicine at the University of South Florida in Tampa. (bloodcancerstoday.com)
Controls were patients with AML who had a history of MDS or CMML and NPM1 mutations detected (n=31). (bloodcancerstoday.com)
These mutations are found across the full spectrum of myeloid neoplasia, including pediatric Down Syndrome-associated acute megakaryoblastic leukemia (DS-AMKL), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and de-novo and secondary acute myeloid leukemia (AML). (dana-farber.org)
Scientists from the Children's Hospital of Philadelphia (CHOP) say they have found how mutations in a protein network drive several high-risk leukemias, particularly chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML), both of which tend to have a poor prognosis because they progress to acute myeloid leukemia (AML). (medicilon.com)
Dr. Tong added that clinical research should test whether this drug can benefit patients with CMML and JMML, as well as AML patients who have CBL mutations. (medicilon.com)

The true incidence of somatic mutations in MDS/MPN overlap syndromes remains uncertain, since these syndromes were previously under-diagnosed. (medscape.com)
In this work, we integrated somatic mutations, transcription, (hydroxy)methylation, histone modifications, and chromatin accessibility to reveal the complexity of the epigenetic landscape, the simultaneous presence of multiple regulatory mechanisms affecting drivers of leukemogenesis, and remodeling of the enhancer landscape as an important driver of intratumoral heterogeneity. (nature.com)
The RUNX1 gene mutations associated with these diseases are somatic mutations and are not inherited. (medlineplus.gov)
When the hierarchy of somatic mutations was analyzed, BCOR mutations were below the known initial mutations (ASXL1 or TET2) but were above U2AF1 mutations. (biomedcentral.com)
Somatic mutations in DNMT3A, TET2, ASXL1, and JAK2 were each individually associated with coronary heart disease. (ascopost.com)
Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. (hunimed.eu)
Unsupervised statistical analysis, including the World Health Organization classification criteria and somatic mutations, showed that MDS associated with SF3B1-mutation (51 of 245 patients, 20.8%) is a distinct nosologic entity irrespective of current morphologic classification criteria. (hunimed.eu)
Irrespective of driver somatic mutations, a threshold of 5% bone marrow blasts retained a significant discriminant value for identifying cases with clonal evolution. (hunimed.eu)
Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. (encyclopedia.pub)
Targeted next-generation sequencing (NGS) of a panel of 80 genes was performed on her initial bone marrow aspirate sample and identified PTPN11, NRAS , and DNMT3A somatic mutations. (frontiersin.org)
Comprehensive genetic testing showed that many molecular variations (including FA gene germline mutations, RAS and epigenetic pathway somatic mutations, and NUP98-HOXC11 fusion) were highly linked to her serious and complex medical history ( Figures 1A, B ). (frontiersin.org)
Risk increases with age due to the acquisition of somatic mutations that can promote clonal expansion and dominance of a particular hematopoietic stem cell, and possibly due to exposure to environmental toxins such as benzene, radiation, and chemotherapeutic agents (particularly long or intense regimens and those involving alkylating agents, hydroxyurea , and/or topoisomerase inhibitors). (msdmanuals.com)
Somatic mutations at the phosphotyrosine-binding pocket of the C-terminal SH2 domain of GTPase-activating protein RASA1 have been found in a subset of Basal-cell carcinoma (BCC) [Friedman, 1995]. (lu.se)

Chronic myeloid neoplasms are malignant clonal hematopoietic stem cell disorders driven by recurrent genetic events, with an inherent risk of transformation to acute myeloid leukemia (AML) 1 , 2 . (nature.com)
The myeloid neoplasms contain acute and chronic leukemias, myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). (wikipedia.org)
The frequencies of dmin in acute myeloid leukemia (AML) range from 0.3% to 2.8% [ 4 ]. (hindawi.com)
DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mutated acute myeloid leukemia (AML) has a poor prognosis, but the exact mechanism is still unclear. (frontiersin.org)
Acute myeloid leukemia (AML) is a common, heterogeneous, and aggressive hematopoietic malignancy, characterized by apparent genetic abnormalities ( 1 ). (frontiersin.org)
Mutations in the ASXL1 gene have been associated with cancerous conditions of blood-forming cells, such as acute myeloid leukemia, chronic myelomonocytic leukemia, and myelodysplastic syndrome. (medlineplus.gov)
Occasionally, the FIP1L1-PDGFRA fusion can be identified in patients with acute myeloid leukemia or B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma and sporadically in myeloid sarcoma (Metzgeroth et al. (atlasgeneticsoncology.org)
Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis that present clinically as cytopenia(s), dysplasia in one or more hematopoietic cell lines in the bone marrow, and risk of transformation to acute myeloid leukemia (AML). (medscape.com)
A rearrangement (translocation) of genetic material involving the RUNX1 gene is found in approximately 7 percent of individuals with a form of blood cancer known as acute myeloid leukemia (AML). (medlineplus.gov)
Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. (medlineplus.gov)
TET2 mutations have been associated with reduced patient survival in acute myeloid leukemia. (aacrjournals.org)
Acute myeloid leukemia (AML) patients with a high allelic burden of an internal tandem duplication ( ITD )-mutated FMS - like Tyrosine Kinase - 3 ( FLT3 ) have a dismal outcome. (biomedcentral.com)
Acute myeloid leukemia (AML) is mainly a fatal disease. (biomedcentral.com)
Around the same time, and building on the observation that the vitamin folic acid could stimulate acute lymphoblastic leukemia (ALL) cells, Farber used folate analogs such as aminopterin and then amethopterin (methotrexate) to treat ALL, in what is often heralded as the first 'rational' drug development approach [ 4 ]. (biomedcentral.com)
Idhifa is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. (pharmaceutical-technology.com)
Dr. Sallman's research focuses on the development of novel, targeted therapeutic strategies for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). (moffitt.org)
Phase I and II clinical trials) for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) based on the underlying mutational drivers of each disease. (moffitt.org)
As an example, Dr. Sallman has focused research and clinical trial efforts on patients who have TP53 mutation (often associated with complex genes/cytogenetics) given their high risk of transformation to acute leukemia and poor survival. (moffitt.org)
The MLL -partial tandem duplication (PTD) associates with high-risk cytogenetically normal acute myeloid leukemia (AML). (ashpublications.org)
A characteristic feature of MDS is an increased risk of transformation into acute myeloid leukemia (AML). (clinlabdia.ru)
Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. (elsevierpure.com)
Attention is focused on clonal myeloid disorders, acute lymphoblastic leukemia, lymphoma, and plasma cell dyscrasias. (ascopost.com)
To define genotype/phenotype relationships of clinical relevance, we studied 308 patients with MDS, MDS/MPN, or acute myeloid leukemia evolving from MDS. (hunimed.eu)
RUNX1 mutations have been reported in approximately 10% of myelodysplastic cases, 5-15% of acute myeloid leukemia, 8-37% of chronic myelomonocytic leukemia, 10% of T cell acute lymphoblastic leukemia, 3% of systemic mastocytosis, 2% of essential thrombocythemia and 2% of polycythemia vera. (cornell.edu)
RUNX1 mutations are independently associated with unfavorable outcomes and shorter survival after hematopoietic stem cell transplantation in patients with myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia. (cornell.edu)
This phase II trial studies how well enasidenib and azacitidine work in treating patients with IDH2 gene mutation and acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). (sparkcures.com)
Clinical course is highly variable, with a median overall survival (OS) that ranges between 12-24 months and 15-30% probability of progression to acute myeloid leukemia (AML) [ 6 ] . (encyclopedia.pub)
Genetic analysis of dasatinib-treated chronic myeloid leukemia rapidly developing into acute myeloid leukemia with monosomy 7 in Philadelphia-negative cells. (lu.se)
A fraction of these patients, in particular those displaying trisomy 8 or monosomy 7, are at risk of developing a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). (lu.se)
FMS-like tyrosine kinase 3 ( FLT3 ) is one of the most frequently mutated genes in acute myeloid leukemia (AML). (dovepress.com)
Acute myeloid leukemia (AML) is a severe heterogeneous group of neoplastic disorders driven by several molecular alterations. (dovepress.com)
The researchers, who presented their findings at the 64th American Society of Hematology Annual Meeting & Exposition, said the results support the World Health Organization's proposal to reclassify these types of MNs into acute myeloid leukemia (AML), regardless of blast counts, so that these patients can benefit from more intensive treatments. (bloodcancerstoday.com)
Like splicing factors, genes encoding components of the cohesin complex are frequently mutated in cancer, including myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML), where they are associated with poor outcomes. (dana-farber.org)
if acute myeloid leukemia supervenes, it is treated per the usual protocols. (msdmanuals.com)

Recurrent somatic BCOR mutations have been identified in myelodysplastic syndrome (MDS). (biomedcentral.com)
RUNX1 nonsense or frameshift mutations are associated with an unfavorable prognosis in myelodysplastic syndrome, independent of IPSS, IPSS-R, age, and other gene mutations (NCCN Guidelines for Myelodysplastic Syndromes). (cornell.edu)

For example, loss of function mutations of the EZH2 gene are seen in around 10% of MDS/MPN cases and are associated with poor prognosis. (medscape.com)
Recurrent mutations in the gene encoding additional sex combs-like 1 ( ASXL1 ) are found in various hematologic malignancies and associated with poor prognosis. (jci.org)
However, the clinical impact of BCOR mutations on MDS prognosis is controversial and the response of hypomethylating agents in MDS with BCOR mutations (BCOR MUT ) remains unknown. (biomedcentral.com)
In clinical analyses, mutations in CBL were associated with adverse prognosis in patients with chronic myelomonocytic leukemia ( PMID: 26230957 , PMID: 23690417 , PMID: 19901108 ). (jax.org)
CBL mutations are associated with an adverse prognosis in patients with systemic mastocytosis (NCCN.org). (jax.org)
RUNX1 mutations are also associated with an unfavorable prognosis chronic myelomonocytic leukemia and systemic mastocytosis. (cornell.edu)
1 , 7-9 In the 2017 European Leukemia network (ELN) classification, prognosis of FLT3 -ITD mutation on the survival of AML patients was dependent on the co-occurrence of the nucleophosmin 1 gene mutation ( NPM1 mut) and the FLT3 -ITD mutation burden. (dovepress.com)

Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. (elsevierpure.com)
No recurrent mutation pattern correlated with unilineage dysplasia without ring sideroblasts. (hunimed.eu)
AML with RUNX1 mutation which does not fulfill the diagnostic criteria for other specific AML subtypes in the categories of AML with recurrent genetic abnormalities, therapy-related myeloid neoplasms, or AML with myelodysplasia-related changes is now classified the provisional entity of AML with mutated RUNX1. (cornell.edu)
Recurrent ETNK1 mutations in atypical chronic myeloid leukemia. (ox.ac.uk)
Despite the recent identification of recurrent SETBP1 mutations in atypical chronic myeloid leukemia (aCML), a complete description of the somatic lesions responsible for the onset of this disorder is still lacking. (ox.ac.uk)
In summary, our study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders. (ox.ac.uk)

Here, we aimed to explore the mechanism of immune escape in AML with DNMT3A mutation. (frontiersin.org)
It relieved the inhibitory effect of DNMT3A mutation, promoted the phenotypic recovery of the co-cultured macrophages, eliminated resistance, and regulated the immune microenvironment. (frontiersin.org)
About 25% of AML cases are accompanied by DNA (cytosine-5)-methyltransferase 3A (DNMT3A) molecular mutation. (frontiersin.org)
For the past several years, efforts have been made to explore functional consequences associated with the DNMT3A mutation. (frontiersin.org)
The DNMT3A mutation can cause significant changes in epigenetic modifications and is one of the essential regulatory factors for the occurrence and development of leukemia ( 4 ). (frontiersin.org)
DNMT3A mutation is an inactivating mutation. (frontiersin.org)
Some researchers believe that DNMT3A mutations cause hypomethylation of the whole genome, and this hypomethylation is often associated with a higher recurrence rate and worse OS ( 8 ). (frontiersin.org)
BCOR mutations were associated with DNMT3A or RUNX1 mutations and were independently associated with worse overall survival (OS). (biomedcentral.com)
Other notable findings were that concurrent baseline DNMT3A mutations tended to be associated with inferior outcomes, and patients who underwent transplantation had better outcomes. (bloodcancerstoday.com)

Canning AJ, Viggiano S, Fernandez-Zapico ME , Cosgrove MS. Parallel functional annotation of cancer-associated missense mutations in histone methyltransferases. (mayo.edu)
Somatic missense mutations in cancer-related genes were detected in three IHES patients. (oncotarget.com)
In 2 cases (13.3%), we identified somatic missense mutations in the ETNK1 gene. (ox.ac.uk)

Myeloid neoplasms, predominantly MDS/AML, developing in patients, usually at a young age, with a familial platelet disorder and germline monoallelic RUNX1 mutations are categorized as myeloid neoplasms with germline RUNX1 mutation. (cornell.edu)
This case highlights the importance of genetic counseling in patients with hematopoietic neoplasms with high clinical suspicion for carrying cancer susceptibility gene mutations, which require timely diagnosis and personalized management. (frontiersin.org)
According to recent research, myeloid neoplasms (MNs) with NPM1 gene mutations are an aggressive subtype. (bloodcancerstoday.com)

Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia. (standuptocancer.org)
Mutations have also been found in the blood of elderly patients without hematopoietic cancers, indicating that TET2 loss alone is not sufficient to trigger leukemic transformation (reviewed in ref. 5 ). (aacrjournals.org)
Genomic studies have uncovered silencing TET2 mutations in B-cell and T-cell lymphomas ( 6-8 ), indicating a tumor suppressor role for TET2 in lymphoid malignancies. (aacrjournals.org)
In this issue of Cancer Discovery , Dominguez and colleagues report their findings on the mechanistic link between TET2 mutation and germinal center (GC) B-cell transformation (3). (aacrjournals.org)
TET2 Mutations Affect Non-CpG Island DNA Methylation at Enhancers and Transcription Factor-Binding Sites in Chronic Myelomonocytic Leukemia. (uchicago.edu)
To generate induced pluripotent stem cell clones, we reprogrammed CD34 + cells collected from a patient with a chronic myelomonocytic leukemia in which whole exome sequencing of peripheral blood monocyte DNA had identified 12 gene mutations, including a mutation in KDM6A and two heterozygous mutations in TET2 in the founding clone and a secondary KRAS (G12D) mutation. (philinbiomed.org)
Comutation of TET2 and SRSF2 was highly predictive of a myeloid neoplasm characterized by myelodysplasia and monocytosis, including but not limited to, chronic myelomonocytic leukemia. (hunimed.eu)

It falls under the group myelodysplastic/myeloproliferative neoplasm with other disorders like atypical chronic myeloid leukemia. (patientworthy.com)

Aberrant differentiation in MDS can often be traced to abnormal DNA methylation as well as mutations in genes that regulate epigenetic programs involved in DNA methylation or histone modification control [ 1 ]. (biomedcentral.com)
Whole-exome sequencing and genome-wide methylation analyses identify novel disease associated mutations and methylation patterns in idiopathic. (oncotarget.com)

These leukemias currently have few treatment options, so identifying the causative gene networks may lead to more effective targeted treatments," said Wei Tong, Ph.D., a hematology researcher whose team published its study ("CBL Family E3 Ubiquitin Ligases Control JAK2 Ubiquitination and Stability in Hematopoietic Stem Cells and Myeloid Malignancies") in Genes & Development . (medicilon.com)
Myelodysplastic syndromes are a group of clonal hematopoietic stem cell disorders unified by the presence of distinct mutations of hematopoietic stem cells, most frequently in genes involved in RNA splicing. (msdmanuals.com)
Less prevalent findings include cryptorchidism in affected boys, mental retardation, bleeding diatheses and hematopoietic abnormalities including certain leukemias [Gelb & Tartaglia, 2006]. (lu.se)

Leukemia subtypes are categorised into single clinical entities so that they can be diagnosed and treated appropriately. (wikipedia.org)
As we continue to discover that specific mutations may cause subtypes of cancer, learning the underlying molecular mechanisms provides opportunities to develop targeted treatments. (medicilon.com)

They tend not to occur in AML cases with favorable cytogenetic findings and appear to be exclusive of NPM1 or CEBPA mutations in AML. (cornell.edu)
Ultimately, 64% of patients with MN and NPM1 mutation transformed to AML in a median 21.1 months. (bloodcancerstoday.com)
Clinical characterization and outcomes of patients with NPM1-mutated myelodysplastic syndromes or chronic myelomonocytic leukemia. (bloodcancerstoday.com)

Non-FA (or underlying FA) patients harboring heterozygous germline FA gene mutations may also face an increased risk of developing bone marrow failure, primary immunodeficiency disease, and hereditary cancer predisposition syndromes. (frontiersin.org)
Whole-exome sequencing (WES) verified RAD51C, BRIP1, PALB2 , and FANCG heterozygous germline mutations of the FA pathway, which were further confirmed in buccal swab samples by Sanger sequencing. (frontiersin.org)

Prognostic score including gene mutations in chronic myelomonocytic leukemia. (jax.org)
Poor Prognostic Implication of ASXL1 Mutations in Korean Patients With Chronic Myelomonocytic Leukemia. (cdc.gov)

We captured a part of the genetic heterogeneity observed in the patient, i.e. we analyzed five clones with two genetic backgrounds, without and with the KRAS (G12D) mutation. (philinbiomed.org)
Given the strong association between monosomy 7 and mutation of genes involved in the RAS pathway in juvenile myelomonocytic leukemia, we also screened for pathogenetic variants in KRAS, NRAS, and PTPN11, but did not detect any changes. (lu.se)
2001]. Another forms of Noonan syndrome are caused by mutations in the KRAS [Schubbert et al. (lu.se)

Truncating mutations in the chromatin remodeler ASXL1 (ASXL1 MT ) are associated with a high-risk disease phenotype with increased proliferation, epigenetic therapeutic resistance, and poor survival outcomes. (nature.com)
In fact, the requirements, under which CHIP mutations become myeloid driver mutations, cooperate with other genetic or epigenetic changes to eventually cause AML, are not well understood. (biomedcentral.com)

In particular, ASXL1 mutations are common in patients with hematologic malignancies associated with myelodysplasia, including myelodysplastic syndromes (MDSs), and chronic myelomonocytic leukemia. (jci.org)
Aberrant NFAT signaling is causally involved in the development of chronic lymphocytic leukemia, non-Hodgkin lymphoma, pancreatic cancer, and several other malignancies. (biomedcentral.com)
Cohesin mutations in myeloid malignancies. (dana-farber.org)

Our data show that a subset of IHES may be of clonal origin not related to the classical molecular aberrations of FGFR, PDGFRA/B , or T-cells, and that the initiating hits could be point mutations in a variety of genes, including spliceosome mutations or hypermethylated tumor suppressor genes. (oncotarget.com)
Clonal hematopoiesis of indeterminate potential carriers with these mutations also had increased coronary artery calcification, a marker of coronary atherosclerosis burden. (ascopost.com)
Targeted resequencing on 515 hematological clonal disorders revealed the presence of ETNK1 variants in 6 (8.8%) of 68 aCML and 2 (2.6%) of 77 chronic myelomonocytic leukemia samples. (ox.ac.uk)
Despite the recent success of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), approximately 2-17% of patients develop clonal cytogenetic changes in the Philadelphia-negative (Ph(-)) cell population. (lu.se)

Clinical features and survival outcomes in patients with chronic myelomonocytic leukemia arising in the context of germline predisposition syndromes. (uchicago.edu)
He has published significantly on this topic including recently in highly regarded journals including Leukemia and Haematologica and these work form the foundation of the clinical trials that he is bringing to patients in order to improve their quality of life and survival. (moffitt.org)
For patients with chronic myelomonocytic leukemia, the overall response rate was higher for azacitidine plus lenalidomide vs azacitidine alone (68% vs 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. (ascopost.com)
CBL mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org). (jax.org)
Although the impact of FLT3 -ITD mutation is unclear in the context of venetoclax-azacitidine treatment, 6 the negative impact of FLT3 -ITD on survival of AML patients treated with ICT is well established. (dovepress.com)

Throughout the lifetime of patients with an FA gene mutation, DNA damage increasing accumulates, which would lead to a complex clinically and genetically heterogeneous disorder characterized by developmental abnormalities, bone marrow failure (BMF), immune deficiency, and a high risk of developing various cancers (e.g. (frontiersin.org)
They had lower bone marrow blast counts than controls and tended to have fewer IDH1/2 and FLT3-ITD/TKD mutations. (bloodcancerstoday.com)

Noonan syndrome (NS) is caused by mutations in PTPN11 , a gene encoding the nonreceptor protein tyrosine phosphatase SHP2. (lu.se)
1999 ]. Germline mutations in PTPN11 lead to Noonan syndrome associated with JMML, and somatic PTPN11 mutations are associated with isolated JMML [Tartaglia et al. (lu.se)

Loss-of-function mutations of ASXL1 , which encodes a protein that recruits the PRC2 complex to the histones, is a driver event in some cases of MDS/MPN. (medscape.com)
Splicing factor mutations alter splicing in different ways and affect the expression of different genes involved in RNA splicing, protein synthesis, and mitochondrial function, suggesting common mechanisms of action in MDS. (medscape.com)
D ) ASXL1 protein expression using C-terminus anti-ASXL1 antibodies in leukemia cell lines. (jci.org)
Most of the ASXL1 gene mutations that cause Bohring-Opitz syndrome create a premature stop signal in the instructions for making the ASXL1 protein, resulting in either an abnormally short, nonfunctional protein or a complete lack of ASXL1 protein. (medlineplus.gov)
These ASXL1 gene mutations are described as "loss-of-function" because they reduce the amount of functional ASXL1 protein available, which likely disrupts the regulation of the activity of HOX genes and other genes during development. (medlineplus.gov)
The mutations associated with these conditions are likely "gain-of-function," which means that they lead to an overactive ASXL1 protein. (medlineplus.gov)
ZAP-70 deficiency is a rare autosomal recessive form of severe combined immunodeficiency (SCID) caused by mutations in the gene coding for T cell receptor z-chain associated protein kinase [ Chan et al. (lu.se)

Patients with FA gene mutation are hypersensitive to DNA damage and unable to successfully repair damaged DNA when exposed to DNA-crosslinking agents, cytotoxic chemotherapeutics, and ionizing radiation ( 3 , 4 ). (frontiersin.org)

0001) and, to a lesser extent, SRSF2 (P = .03), CBL (P = .003), and IDH2 (P = .03) mutations predicted inferior OS in univariable analysis. (jax.org)

An interstitial deletion del(4)(q12q12) generating a FIP1L1-PDGFRA fusion gene is observed in diverse eosinophilia-associated hematologic disorders like hyperseosinophilic syndrome (HES), systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL). (atlasgeneticsoncology.org)

ASXL1-MT mice displayed features of human-associated MDS, including multi-lineage myelodysplasia, pancytopenia, and occasional progression to overt leukemia. (jci.org)

The ASXL1 gene mutations involved in these cancers are different from the ones that cause Bohring-Opitz syndrome (described above). (medlineplus.gov)
(B) The patient was born with four Fanconi anemia (FA) gene mutations and germline predisposition to cancers. (frontiersin.org)
See Chronic Leukemias: 4 Cancers to Differentiate, a Critical Images slideshow, to help detect chronic leukemias and determine the specific type present. (medscape.com)

However, mice expressing either Mll -PTD or Flt3 -ITD do not develop AML, suggesting that 2 mutations are necessary for the AML phenotype. (ashpublications.org)
A significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation. (ascopost.com)
The treatment paradigm of AML patients harboring FLT3 mutations (30%) has been modified by the discovery of tyrosine kinase inhibitors. (dovepress.com)
Activity of these inhibitors depends on their mechanism of receptor binding (active vs inactive conformation) and efficacy against the FLT3-ITD and -TKD mutations (type 1 inhibitors are active both on FLT3 -ITD and TKD, whereas type 2 inhibitors are active only on FLT3 -ITD). (dovepress.com)

This question is addressed in chronic myelomonocytic leukemia, a myeloid neoplasm in which clinical diversity contrasts with limited genetic heterogeneity. (philinbiomed.org)
These analyses suggest that, beyond the coding mutations, several levels of intraclonal heterogeneity may participate in the yet unexplained clinical heterogeneity of the disease. (philinbiomed.org)
These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. (encyclopedia.pub)
The clinical manifestations of CML are insidious, changing somewhat as the disease progresses through its 3 phases (chronic, accelerated, and blast). (medscape.com)

RUNX1 mutations may be associated with Trisomy 8 or MLL-PTD in AML according to some studies. (cornell.edu)

2003]. The disorder can also be caused by mutations in NRAS , KRAS2 , NF1 , or GRAF . (lu.se)

The index case-patient was a 57-year-old man with chronic lymphocytic leukemia who had been occupationally exposed to poultry. (cdc.gov)

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate. (medscape.com)
Treatment protocols for chronic myelogenous leukemia are provided below for chronic phase, accelerated phase, and blast phase. (medscape.com)

Our data provide evidence for an axis of MDS pathogenesis that implicates both ASXL1 mutations and miR-125a as therapeutic targets in MDS. (jci.org)
Molecular pathogenesis of core binding factor leukemia: current knowledge and future prospects. (medlineplus.gov)

An existing drug might be repurposed to treat these leukemias, and the new understanding of the molecular mechanisms at work may offer clues to other drugs yet to be developed, according to that investigators. (medicilon.com)

26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. (elsevierpure.com)

however chronic eosinophilic leukemia with FIP1L1-PDGFRA is likely to be responsive also to dasatinib, nilotinib, sorafenib and midostaurin (PKC412) (Lierman et al. (atlasgeneticsoncology.org)
the T674I mutation in the ATP-binding region of PDGFRA (mutation of the threonine at position 674) is the most common. (atlasgeneticsoncology.org)

[ 8 ] was renamed in the 2022 WHO classification to MDS/MPN with SF3B1 mutation and thrombocytosis, due to evolving understanding of disease biology. (medscape.com)
SF3B1 mutations are found in 28% of MDS cases overall and in over 80% of cases of with increased ring sideroblasts. (medscape.com)
10%). The co-occurrence of SF3B1 with an MPN driver mutation strongly supports this diagnosis and likely accounts for its mixed MDS/MPN phenotype. (medscape.com)
Here, we show that cohesin mutations are biomarkers of sensitivity to drugs targeting the splicing-factor SF3B1 (H3B-8800 and E-7107). (dana-farber.org)
Myelodysplastic syndromes with low blasts and isolated 5q deletion, MDS with low blasts and SF3B1 mutation, and MDS with biallelic TP53 inactivation were listed under MDS with defined genetic abnormalities. (rarediseaseadvisor.com)

If omics-based assays were applied with appropriate study designs, thorough validation of the markers, and careful interpretation of study results then a bioinformatics database could be built of the human response to different chemical exposures and associated chronic diseases. (who.int)

Here we demonstrate that C-terminal-truncating Asxl1 mutations (ASXL1-MTs) inhibited myeloid differentiation and induced MDS-like disease in mice. (jci.org)

ASXL1 mutations inhibit G-CSF-induced myeloid differentiation of 32Dcl3 cells. (jci.org)
P = .01 and P = .0008, respectively), suggesting that ETNK1 mutations may inhibit the catalytic activity of the enzyme. (ox.ac.uk)

Anatomy30

Organisms17

Diseases50

Chemicals and Drugs55

Analytical, Diagnostic and Therapeutic Techniques and Equipment38

Phenomena and Processes78

Disciplines and Occupations2

Information Science5

Health Care6

CMML24

Somatic mutations13

Acute34

Myelodysplastic syndrome2

Prognosis7

Recurrent6

DNMT3A9

Missense3

Neoplasms3

TET27

Myeloproliferative neoplasm1

Methylation2

Hematopoietic3

Subtypes2

NPM13

Heterozygous2

Prognostic2

KRAS3

Epigenetic2

Malignancies3

Clonal4

Survival5

Bone Marrow2

PTPN112

Protein7

Gene mutation1

IDH21

Systemic mastocytosis1

ASXL1 MT1

Cancers3

FLT34

Clinical4

RUNX11

NRAS1

Lymphocytic leukemia1

Myelogenous leukemia2

Pathogenesis2

Molecular1

EZH21

PDGFRA2

SF3B15

Diseases1

Disease1

Inhibit2