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BIOMARKER:

ASXL1 Y588X

i
Other names: ASXL1, ASXL Transcriptional Regulator 1, Additional Sex Combs Like 1, Transcriptional Regulator, Polycomb Group Protein ASXL1, Additional Sex Combs Like Transcriptional Regulator 1, Additional Sex Combs Like 1 (Drosophila), Putative Polycomb Group Protein ASXL1, Additional Sex Combs-Like Protein 1, KIAA0978, BOPS, MDS
Entrez ID:
Related biomarkers:
12ms
Targeting lysine demethylase 6B ameliorates ASXL1 truncation-mediated myeloid malignancies in preclinical models. (PubMed, J Clin Invest)
Importantly, administration of GSK-J4, a KDM6B inhibitor, not only restored H3K27me3 levels but also reduced the disease burden in NSG mice xenografted with human ASXL1 mutant leukemic cells in vivo. This preclinical finding provides compelling evidence that targeting KDM6B may be a therapeutic strategy for myeloid malignancies with ASXL1 mutations.
Preclinical • Journal
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ASXL1 (ASXL Transcriptional Regulator 1) • KDM6B (Lysine Demethylase 6B)
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ASXL1 mutation • ASXL1 Y588X
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GSKJ4
12ms
ASXL1 mutations are associated with a response to alvocidib and 5-azacytidine combination in myelodysplastic neoplasms. (PubMed, Haematologica)
The higher sensitivity of ASXL1 mutant cells to the combination treatment was confirmed in vivo in ASXL1Y588X transgenic mice. Overall, our study demonstrated augmented activity for the alvocidib + 5-AZA combination in higher-risk MDS and identified ASXL1 mutations as a biomarker of response for potential stratification studies.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • ASXL1 (ASXL Transcriptional Regulator 1) • MCL1 (Myeloid cell leukemia 1) • CDK9 (Cyclin Dependent Kinase 9)
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ASXL1 mutation • ASXL1 Y588X
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azacitidine • alvocidib (DSP-2033)
almost2years
ASXL1 Mutations Are Associated with a Response to the Combination of Alvocidib and 5-Azacytidine in Higher-Risk Myelodysplastic Syndromes (ASH 2022)
A phase 1b/2 study with Alv and HMAs 5-Azacytidine (5-AZA) or decitabine in higher-risk MDS patients was recently completed (NCT03593915). We provided a pre-clinical rationale for the use of the 5-AZA+Alv combination for higher risks MDS and proposed ASXL1 mutations as potential genetic biomarkers of response in prospective clinical trials.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • ASXL1 (ASXL Transcriptional Regulator 1) • MCL1 (Myeloid cell leukemia 1) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CDK9 (Cyclin Dependent Kinase 9) • ANXA5 (Annexin A5)
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ASXL1 mutation • MCL1 expression • ASXL1 Y588X
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azacitidine • decitabine • alvocidib (DSP-2033)