SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS

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Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-Am...

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Impact of TET2, SRSF2, ASXL1 and SETBP1 mutations on survival of patients with chronic myelomonocytic leukemia

BACKGROUND Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm classified in the myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category. Molecular abnormalities are reported in about 90 % of patients with CMML. ASXL1 and SETBP1 mutations, but not TET2 or SFRS2 mutations are reported to be associated with prognosis. METHODS We studied frequency of TET2, SRSF2, ASXL1 a...

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Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS

Isolated isochromosome 17q, i(17q), accounts for less than 1% of myeloid neoplasms that are commonly classified as myelodysplastic/myeloproliferative neoplasms, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). We have shown previously that these cases have distinctive clinicopathologic features, a poor prognosis and absence of TP53 mutations. H...

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Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation.

Inherited or sporadic heterozygous mutations in the transcription factor GATA2 lead to a clinical syndrome characterized by non-tuberculous mycobacterial and other opportunistic infections, a severe deficiency in monocytes, B cells and natural killer cells, and progression from a hypocellular myelodysplastic syndrome to myeloid leukemias. To identify acquired somatic mutations associated with m...

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ASXL1 is the obligate regulatory subunit of a deubiquitinase complex whose catalytic subunit is BAP1. Heterozygous mutations of ASXL1 that result in premature truncations are frequent in myeloid leukemias and Bohring-Opitz syndrome. Here we demonstrate that ASXL1 truncations confer enhanced activity on the ASXL1-BAP1 complex. Stable expression of truncated, hyperactive ASXL1-BAP1 complexes in a...

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ژورنال

عنوان ژورنال: Leukemia

سال: 2014

ISSN: 0887-6924,1476-5551

DOI: 10.1038/leu.2014.301