Genomic Characteristics and Prognostic Significance of Co-mutated ASXL1/SRSF2 Acute Myeloid Leukemia.

Abstract:

:ASXL1 and SRSF2 mutations in AML are frequently found in patients with preexisting myeloid malignancies and are individually associated with poor outcomes. In this multi-institutional retrospective analysis, we assessed the genetic features and clinical outcomes of 43 patients with ASXL1mut SRSF2mut AML and compared outcomes to patients with either ASXL1 (n=57) or SRSF2 (n=70) mutations. Twenty-six (60%) had secondary-AML (s-AML). Variant allele fractions suggested that SRSF2 mutations preceded ASXL1 mutational events. Median overall survival (OS) was 7.0 months (95% CI:3.8,15.3) and was significantly longer in patients with de novo versus s-AML (15.3 versus 6.4 months, respectively; p=0.04 on adjusted analysis). Compared to ASXL1mut SRSF2wt and ASXL1wt SRSF2mut , co-mutated patients had a 1.4 and 1.6 times increase in the probability of death, respectively (p=0.049), with a trend towards inferior OS (median OS = 7.0 vs. 11.5 vs. 10.9 months, respectively; p =0.10). Multivariable analysis suggests this difference in OS is attributable to the high proportion of s-AML patients in the co-mutated cohort (60% vs. 32% and 23%, respectively). Although this study is limited by the retrospective data collection and the relatively small sample size, these data suggest that ASXL1mut SRSF2mut AML is a distinct subgroup of AML frequently associated with s-AML and differs from ASXL1mut SRSF2wt /ASXL1wt SRSF2mut with respect to etiology and leukemogenesis. This article is protected by copyright. All rights reserved.

journal_name

Am J Hematol

authors

Richardson DR,Swoboda DM,Moore DT,Johnson SM,Chan O,Galeotti J,Esparza S,Hussaini MO,Van Deventer H,Foster MC,Coombs CC,Montgomery ND,Sallman DA,Zeidner JF

doi

10.1002/ajh.26110

subject

Has Abstract

pub_date

2021-01-27 00:00:00

eissn

0361-8609

issn

1096-8652

pub_type

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