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BIOMARKER:

SETBP1 mutation

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Other names: SETBP1, SET Binding Protein 1, SET-Binding Protein, SEB, MRD29
Entrez ID:
Related biomarkers:
2ms
First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis. (PubMed, Blood)
Clinically, a striking difference in disease aggressiveness was noted, with SETBP1-mutated patients showing a much worse clinical course. As opposite to myelodysplastic/myeloproliferative neoplasms, where SETBP1 mutations are mostly found as a late clonal event, single-cell clonal hierarchy reconstruction in three TN-PMF patients from our cohort revealed SETBP1 to be a very early event, suggesting that the phenotype of the different SETBP1+ disorders may be shaped by the opposite hierarchy of the same clonal SETBP1 variants.
Journal
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SETBP1 (SET Binding Protein 1)
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SETBP1 mutation • SETBP1 expression
3ms
Journal
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ASXL1 (ASXL Transcriptional Regulator 1) • CSF3R (Colony Stimulating Factor 3 Receptor) • SETBP1 (SET Binding Protein 1)
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ASXL1 mutation • SETBP1 mutation
4ms
Comprehensive genomic profiling reveals molecular subsets of ASXL1-mutated myeloid neoplasms. (PubMed, Leuk Lymphoma)
STAG2 and SETBP1 mutations were also exclusive in ASXL1/SRSF2 co-mutated patients and associated with divergent chronic myeloid phenotypes. Our findings support that certain multi-mutant genotypes may be biologically relevant in ASXL1-mutated myeloid disease.
Journal
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RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • CUX1 (cut like homeobox 1)
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ASXL1 mutation • SF3B1 mutation • CBL mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • SETBP1 mutation
5ms
Efficacy of Demethylated Drug Combine with Low Dose Chemotherapy in Juvenile Myelomonocytic Leukemia (ASH 2023)
All patients were given Demethylated drug in combination with low-dose chemotherapy, 10 patients decitabine at a dose of 20 mg/m2 for 5 days, supplemented with cytarabine (50-100 mg/m2×3~5 days), and /or etoposide (50 mg/m2×3~5 days), 6 patients Azacytidine at a dose of 75mg/m2 for 7 days combined with homoharringtonine 2mg/m2 for 5-7 days. Demethylated drug in combination with low-dose chemotherapy could reduce JMML patients' tumor burden, improve the general condition, and obtain a clinical response rate of 81.8% after 3 cycles therapy. Therefore, such a combination regimen could be used as a therapeutic option for JMML before HSCT.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • JAK3 (Janus Kinase 3) • SETBP1 (SET Binding Protein 1) • SH2B3 (SH2B Adaptor Protein 3)
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KRAS mutation • NRAS mutation • ARID1A mutation • NF1 mutation • ASXL1 mutation • PTPN11 mutation • SRSF2 mutation • SETBP1 mutation • JAK3 mutation
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cytarabine • azacitidine • etoposide IV • decitabine • Synribo (omacetaxine mepesuccinate)
6ms
The impact of SETBP1 mutations in neurological diseases and cancer. (PubMed, Genes Cells)
However, the physiological role of SETBP1 and the molecular mechanisms by which the mutations lead to disease progression have not yet been fully elucidated. In this review, we will describe the current epidemiological data on SETBP1 mutations and shed light on the current knowledge about the SET-dependent and -independent functions of SETBP1.
Review • Journal
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SETBP1 (SET Binding Protein 1) • SET (SET Nuclear Proto-Oncogene)
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SETBP1 mutation
7ms
SETBP1 is dispensable for normal and malignant hematopoiesis. (PubMed, Leukemia)
Contrary to the evidence that SETBP1 mutations are restricted to myeloid malignancies, dependency on SETBP1 mRNA expression is not observed in AML. These unexpected results shed light on the unrecognized idea that a physiologically nonessential gene can act as an oncogene when the machinery of protein degradation is damaged.
Journal
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SETBP1 (SET Binding Protein 1) • VAV1 (Vav Guanine Nucleotide Exchange Factor 1)
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SETBP1 mutation
7ms
SETBP1 mutation determines sensitivity to immune checkpoint inhibitors in melanoma and NSCLC. (PubMed, Aging (Albany NY))
Additional immunological analyses revealed that favorable immune infiltration, tumor immunogenicity, and immune response circuits were enriched in SETBP1-MUT patients. Overall, our findings suggest that SETBP1 mutations may serve as a new biomarker for stratifying beneficiaries of ICI treatments in melanoma and NSCLC, which provides possible evidence for tailoring clinical immunotherapeutic strategies.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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SETBP1 (SET Binding Protein 1)
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SETBP1 mutation
8ms
Co-occurring mutations in ASXL1, SRSF2, and SETBP1 define a subset of myelodysplastic/ myeloproliferative neoplasm with neutrophilia. (PubMed, Leuk Res)
We propose that the presence of co-occurring ASXL1, SRSF2, and SETBP1 mutations can be diagnostic of a subtype of MDS/MPN with neutrophilia if clinical and morphological findings align. Our report underscores the association between genotype and phenotype within MDS/MPN and that genomic signatures should guide categorization of these entities.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1) • CD7 (CD7 Molecule)
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ASXL1 mutation • SRSF2 mutation • SETBP1 mutation • CD7 expression
10ms
TRISOMY 18 IN MYELODYSPLASTIC SYNDROMES (EHA 2023)
The mechanistic basis of MDS remain largely unknown, despite the identification of recurrent cytogenetic abnormalities as well as the discovery of various gene mutations mediating MDS pathogenesis and progression. Isolated trisomy 18 (as well as the cases of other various chromosomal aberrations) is very rare and uncommon in MDS. Three genes located at chromosome 18 may be involved in the pathogenesis of MDS associated to trisomy 18: BCL2, SETBP1 and SMAD4.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • SMAD4 (SMAD family member 4) • SETBP1 (SET Binding Protein 1) • TGFB1 (Transforming Growth Factor Beta 1)
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SETBP1 mutation
10ms
Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis. (PubMed, Orphanet J Rare Dis)
The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.
Journal
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SETBP1 (SET Binding Protein 1)
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SETBP1 mutation • SETBP1 expression
over1year
Accumulation of Specific Somatic Leukemia-Associated Mutations in Congenital Neutropenia Precedes Malignant Transformation – New Preconditions for Treatment Decisions (ASH 2022)
Taken together, CN per se contributes to high level of CH already in the young age, as compared to healthy population. Acquisition of multiple genetic lesions, especially RUNX1, SETBP1, ASXL1, TP53, PTPN11 in association with CSF3R mutation might be a strong indicator of the advanced pre-leukemia stage in CN patients at neutropenia stage and requires closer patient follow up.
Tumor Mutational Burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CSF3R (Colony Stimulating Factor 3 Receptor) • ARID1B (AT-Rich Interaction Domain 1B) • SETBP1 (SET Binding Protein 1) • GNAS (GNAS Complex Locus) • FOXP1 (Forkhead Box P1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • IDH1 mutation • ASXL1 mutation • SETBP1 mutation • CSF3R mutation
almost2years
Mutant-SETBP1 activates transcription of Myc programs to accelerate CSF3R-driven myeloproliferative neoplasms. (PubMed, Blood)
This upregulation of Myc can be reversed by LSD1 inhibitors. In summary, we find that SETBP1 mutations promote aggressive hematopoietic cell expansion when expressed with mutant CSF3R through the upregulation of Myc-associated gene expression programs.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CSF3R (Colony Stimulating Factor 3 Receptor) • SETBP1 (SET Binding Protein 1)
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MYC expression • SETBP1 mutation
almost2years
Chronic neutrophilic leukemia complicated with monoclonal gammopathy of undetermined significance: A case report and literature review. (PubMed, J Clin Lab Anal)
Chronic neutrophilic leukemia may be more inclined to coexist with plasma cell disorder. The CSF3R mutation in CNL-PCD is still the most common mutated gene compared with isolated CNL. Mutations in SETBP1 and ASXL1 may be poor prognostic factors for CNL-PCD.
Clinical • Observational data • Retrospective data • Review • Clinical Trial,Phase II • Journal
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NRAS (Neuroblastoma RAS viral oncogene homolog) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CSF3R (Colony Stimulating Factor 3 Receptor) • SETBP1 (SET Binding Protein 1)
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RUNX1 mutation • ASXL1 mutation • SETBP1 mutation • CSF3R T618I
over2years
Comprehensive Genomic Characterization of ASXL1 C.1934dupG (p.G646fs*12) Versus Other ASXL1 mutations in Myeloid Neoplasia (ASH 2021)
Our results confirm the ASXL1 c.1934dupG variant occurs in a similar patient population to other ASXL1 mutations, and further supports its pathogenicity in myeloid neoplasia. Subset analysis suggests that ASXL1 c.1934dupG and ASXL1 other may be associated with certain phenotypic and co-mutational tendencies. Thus, ASXL1 mutation site may be an important variable in some patients and should be considered in future mechanistic and clinical studies.
TP53 (Tumor protein P53) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)
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TP53 mutation • ASXL1 mutation • KMT2A rearrangement • MLL rearrangement • STAG2 mutation • SETBP1 mutation
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FoundationOne® Heme CDx
over2years
Distinct Mutation Landscapes Between Acute Myeloid Leukemia With Myelodysplasia-Related Changes and De Novo Acute Myeloid Leukemia. (PubMed, Am J Clin Pathol)
The presence of AML-MRC-related mutations can reveal a subset of patients with de novo AML similar to patients with AML-MRC.
Journal
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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1)
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TP53 mutation • ASXL1 mutation • SRSF2 mutation • U2AF1 mutation • SETBP1 mutation
almost3years
Adverse Impact of DNA Methylation Regulatory Gene Mutations on the Prognosis of AML Patients in the 2017 ELN Favorable Risk Group, Particularly Those Defined by NPM1 Mutation. (PubMed, Diagnostics (Basel))
Our results suggest that DMRGM adversely impact the outcomes of ELN favorable group patients, particularly those with mutated NPM1. Further studies are warranted to confirm our observations.
Clinical • Journal • Epigenetic controller
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SETBP1 (SET Binding Protein 1)
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NPM1 mutation • DNMT3A mutation • TET2 mutation • SETBP1 mutation
almost3years
CSF3R T618I, SETBP1 G870S, SRSF2 P95H, and ASXL1 Q780* tetramutation co-contribute to myeloblast transformation in a chronic neutrophilic leukemia. (PubMed, Ann Hematol)
The patient did not use a JAK-STAT pathway inhibitor (ruxolitinib) but started on hydroxyurea and alpha-interferon and developed pruritus after 4 months of diagnosis and nasal hemorrhage 1 month later. We repeated NGS and found that three additional mutations were detected: ASXL1, PRKDC, MYOM2; variant allele frequency (VAF) of the prior mutations in CSF3R, SETBP1, and SRSF2 increased. The concurrence of CSF3RT618I, ASXL1, SETBP1, and SRSF2 mutation may be a mutationally detrimental combination and contribute to disease progression and AML transformation, as well as the nonspecific treatment of hydroxyurea and alpha-interferon, but the significance and role of PRKDC and MYOM2 mutations were not undetermined.
Journal
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NRAS (Neuroblastoma RAS viral oncogene homolog) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1) • CALR (Calreticulin) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
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ASXL1 mutation • SRSF2 mutation • U2AF1 mutation • SETBP1 mutation • CSF3R T618I • SRSF2 P95H • PRKDC mutation
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Jakafi (ruxolitinib) • hydroxyurea
almost3years
Mutant SETBP1 enhances NRAS-driven MAPK pathway activation to promote aggressive leukemia. (PubMed, Leukemia)
Cells expressing NRAS and SETBP1 are sensitive to inhibitors of the MAPK pathway, and treatment with the MEK inhibitor trametinib conferred a survival benefit in a mouse model of NRAS/SETBP1-mutant disease. Our data demonstrate that despite driving enhanced MAPK signaling, SETBP1-mutant cells remain susceptible to trametinib in vitro and in vivo, providing encouraging preclinical data for the use of trametinib in SETBP1-mutant disease.
Journal
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NRAS (Neuroblastoma RAS viral oncogene homolog) • SETBP1 (SET Binding Protein 1)
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NRAS mutation • SETBP1 mutation
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Mekinist (trametinib)
almost3years
Clinicopathologic correlates and natural history of atypical chronic myeloid leukemia. (PubMed, Cancer)
aCML is characterized by high frequencies of ASXL1, SRSF2, and SETBP1 mutations and is associated with a high risk of acute myeloid leukemia transformation. Response and survival outcomes with current therapies remain poor. The incorporation of age, platelet counts, bone marrow blast percentages, and LDH levels can allow survival prediction, and allogeneic stem cell transplantation should be considered for all eligible patients.
Clinical • Journal
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ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1) • GATA2 (GATA Binding Protein 2)
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ASXL1 mutation • TET2 mutation • SRSF2 mutation • SETBP1 mutation
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Jakafi (ruxolitinib)