specific somatic mutations of this gene were discovered in patients affected by atypical Chronic Myeloid Leukemia (aCML) and related diseases. (wikipedia.org)
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)
SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel-Giedion syndrome. (nih.gov)
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)
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)
TMB is a biomarker that measures the number of somatic mutations present in a cancer patient's tumor and is quantified as mutations per megabase (mut/Mb). (cegat.com)
Genes6
In this study, we report the results of a screening for mutations in SETBP1 and JAK3 of a cohort of seventy Italian patients with JMML, identifying 11.4% of them harboring secondary mutations in these two genes and discovering two new mutations in the SKI domain of SETBP1 . (oncotarget.com)
Co-expression of two mutant genes increased myeloid stem cells in animal model, suggesting that cooperation of RUNX1 and ASXL1 mutations played a critical role in leukemia transformation. (biomedcentral.com)
Genes controlled by SETBP1 such as MECOM are significantly upregulated in leukemias containing SETBP1 mutations. (nih.gov)
Gene ontology analysis of deregulated SETBP1 target genes indicates that they are also key controllers of visceral organ development and brain morphogenesis. (nih.gov)
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)
Atypical chronic myeloid1
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)
U2AF12
Correlation between U2AF1 Gene Mutation Characteristics and Clinical Manifestations and Prognosis in Patients with Myelodysplastic Syndrome]. (cdc.gov)
U2AF1 expression is a novel and independent prognostic indicator of childhood T-lineage acute lymphoblastic leukemia. (cdc.gov)
ASXL118
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)
We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1 MT in chronic myelomonocytic leukemia (CMML). (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)
Additional sex combs-like 1 ( ASXL1 ) mutations have been described in all forms of myeloid neoplasms including chronic myelomonocytic leukemia (CMML) and associated with inferior outcomes, yet the molecular pathogenesis of ASXL1 mutations ( ASXL1 -MT) remains poorly understood. (biomedcentral.com)
Previously, we observed that transcription factor RUNX1 mutations ( RUNX1 -MT) coexisted with ASXL1 -MT in CMML and at myeloid blast phase of chronic myeloid leukemia. (biomedcentral.com)
The contribution of RUNX1 mutations in the pathogenesis of myeloid transformation in ASXL1 -mutated leukemia, however, remains unclear. (biomedcentral.com)
At 9 months post-BMT, mice harboring combined RUNX1 and ASXL1 mutations developed disease characterized by marked splenomegaly, hepatomegaly, and leukocytosis with a shorter latency. (biomedcentral.com)
Mice transduced with both ASXL1 and RUNX1 mutations enhanced inhibitor of DNA binding 1 (ID1) expression in the spleen, liver, and bone marrow cells. (biomedcentral.com)
Bone marrow samples from CMML showed that ID1 overexpressed in coexisted mutations of RUNX1 and ASXL1 compared to normal control and either RUNX1 -MT or ASXL1 -MT samples. (biomedcentral.com)
The present study demonstrated the biological and functional evidence for the critical role of RUNX1 -MT in ASXL1 -mutated leukemia in the pathogenesis of myeloid malignancies. (biomedcentral.com)
CSF3R T618I, SETBP1 G870S, SRSF2 P95H, and ASXL1 Q780* tetramutation co-contribute to myeloblast transformation in a chronic neutrophilic leukemia. (cdc.gov)
ASXL1 mutations have been reported in 40-50% of chronic myelomonocytic leukemia(CMML), 20% of myelodsyplastic syndromes, 20-35% of primary myelofibrosis, 15% of systemic mastocytosis, 30% of patients with secondary acute myeloid leukemia and 5-10% of primary acute myeloid leukemia. (cornell.edu)
ASXL1 mutations have also been described in CHIP and CCUS. (cornell.edu)
In CMML, missense mutations of ASXL1 appear to be less common (less than 10% of cases). (cornell.edu)
Nonsense and frameshift mutations (but apparently not missense mutations) of ASXL1 have been reported to carry an adverse prognostic impact in cases of chronic myelomonocytic leukemia. (cornell.edu)
In addition, ASXL1 mutations have been associated with adverse outcome in myelodysplasia, primary myelofibrosis and systemic mastocytosis. (cornell.edu)
Among cases of AML, ASXL1 mutations appear to be associated with adverse prognosis in some subtypes of AML according to some, but not all, studies. (cornell.edu)
While in AML, ASXL1 mutations have been reported to be exclusive of NPM1 mutations according to some studies. (cornell.edu)
RUNX12
Mutational landscape of patients with acute myeloid leukemia or myelodysplastic syndromes in the context of RUNX1 mutation. (cdc.gov)
BCOR mutations were associated with DNMT3A or RUNX1 mutations and were independently associated with worse overall survival (OS). (biomedcentral.com)
Acute11
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)
OBJECTIVE: There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). (bvsalud.org)
In TP53 wild-type acute myeloid leukemia (AML), inhibition of MDM2 can enhance p53 protein expression and potentiate leukemic cell apoptosis. (bvsalud.org)
BACKGROUND: Venetoclax in combination with hypomethylating agents (HMAs) is standard-of-care in patients with newly diagnosed acute myeloid leukemia (AML) who are ≥ 75 years old or unfit for intensive chemotherapy. (bvsalud.org)
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)
High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG). (cdc.gov)
Monitoring of clonal evolution of acute myeloid leukemia identifies the leukemia subtype, clinical outcome and potential new drug targets for post-remission strategies or relapse. (cdc.gov)
Defining Acute Myeloid Leukemia Ontogeny in Older Patients. (cdc.gov)
Clinical analysis of 12 cases of acute myeloid leukemia complicated with synchronous primary solid tumor]. (cdc.gov)
BACKGROUND: In patients with acute myeloid leukemia (AML) a combination of methods must be used to classify the disease, make therapeutic decisions, and determine the prognosis. (gsea-msigdb.org)
Chronic2
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)
Tyrosine kinase inhibitors (TKIs) as first-line therapy for Chronic Myeloid Leukemia (CML) show a high success rate. (biomedcentral.com)
Malignancies1
In summary, this work unveils a SETBP1 function that directly affects gene transcription and clarifies the mechanism operating in myeloid malignancies and in the Schinzel-Giedion syndrome caused by SETBP1 mutations. (nih.gov)
Gene mutations1
Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results. (cdc.gov)
Oncogene1
The clustering was driven by the presence of chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular genetic mutations (CEBPA), and abnormal oncogene expression (EVI1). (gsea-msigdb.org)
Prognosis2
Mutations in SETBP1 and JAK3 were recently identified in a subset of JMML patients characterized by poor prognosis and progression of disease. (oncotarget.com)
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)
Epigenetic1
Here we show that SETBP1 binds to gDNA in AT-rich promoter regions, causing activation of gene expression through recruitment of a HCF1/KMT2A/PHF8 epigenetic complex. (nih.gov)
BCOR6
Clinical Characteristics and Prognostic Significance of BCOR/BCORL1 Gene Mutation in Patients with Myelodysplastic Syndromes]. (cdc.gov)
Recurrent somatic BCOR mutations have been identified in myelodysplastic syndrome (MDS). (biomedcentral.com)
A higher frequency of BCOR mutations (8.7%) was investigated in patients with normal chromosome, compared to 4.2% in patients with abnormal karyotype ( p = 0.040). (biomedcentral.com)
BCOR mutations occur more frequently in CN MDS patients, predicting higher risk of leukemia transformation. (biomedcentral.com)
In this assay, the similarities and differences of the BCOR mutation features of a large cohort (676 total patients) of Chinese MDS patients were analyzed and compared to the results in the existing literature. (biomedcentral.com)
Methylation1
SETBP1 is a DNA-binding protein that forms part of a group of proteins that act together on histone methylation to make chromatin more accessible and regulate gene expression. (wikipedia.org)
Myelodysplastic syndrome1
Clinical analysis of gene mutation characteristics and mutation burden in myelodysplastic syndrome]. (cdc.gov)
Significantly1
The response was associated with immune cell abundance and induced the proteomic profiles of leukemia cells to disrupt survival pathways and significantly reduced MCL1 and YTHDF2 to potentiate leukemic cell death. (bvsalud.org)
Protein4
SET binding protein 1 is a protein that in humans is encoded by the SETBP1 gene. (wikipedia.org)
The SETBP1 gene provides instructions for making a protein known as the SET binding protein 1, which is widely distributed throughout somatic cells. (wikipedia.org)
There is still more to learn about the overall function of the SETBP1 protein and the effect of SET binding. (wikipedia.org)
These mutations, which are identical to the ones present in SGS as germ line mutations, impair the degradation of SETBP1 and therefore cause increased cellular levels of the protein. (wikipedia.org)
Chromosome1
A number sign (#) is used with this entry because pachyonychia congenita-4 (PC4) is caused by heterozygous mutation in the KRT6B gene (148042) on chromosome 12q13. (findzebra.com)
Assay1
JMML xenotransplantation and colony assay provide an initial understanding of the secondary nature of these events occurring in early precursor cells and suggest a different propagating capacity of clones harboring particular mutations. (oncotarget.com)
TP531
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)
Pathways1
Driver mutations in the Ras signaling pathways are a key feature of JMML patients. (oncotarget.com)
Clinical1
These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. (encyclopedia.pub)
Deletion1
Deletion of two AT-hooks abrogates the binding of SETBP1 to gDNA and impairs target gene upregulation. (nih.gov)
Juvenile1
Juvenile myelomonocytic leukemia (JMML) is a rare aggressive disease of early childhood. (oncotarget.com)
Analysis1
Single-cell proteomic analysis of the leukemia compartment revealed therapy-induced proteomic alterations and potential mechanisms of adaptive response to the MDM2i combination. (bvsalud.org)
Function1
Gain-of-function mutations in the SETBP1 gene are associated with Schinzel-Giedion syndrome. (wikipedia.org)