Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome
- 10 May 2012
- journal article
- Published by American Society of Hematology in Blood
- Vol. 119 (19), 4480-4485
- https://doi.org/10.1182/blood-2011-11-390252
Abstract
Leukemic transformation (LT) of myeloproliferative neoplasms (MPNs) is associated with a poor prognosis and resistance to therapy. Although previous candidate genetic studies have identified mutations in MPN patients who develop acute leukemia, the complement of genetic abnormalities in MPN patients who undergo LT is not known nor have specific molecular abnormalities been shown to have clinical relevance in this setting. We performed high-throughput resequencing of 22 genes in 53 patients with LT after MPN to characterize the frequency of known myeloid mutations in this entity. In addition to JAK2 and TET2 mutations, which occur commonly in LT after MPN, we identified recurrent mutations in the serine/arginine-rich splicing factor 2 (SRSF2) gene (18.9%) in acute myeloid leukemia (AML) transformed from MPNs. SRSF2 mutations are more common in AML derived from MPNs compared with LT after myelodysplasia (4.8%) or de novo AML (5.6%), respectively (P = .05). Importantly, SRSF2 mutations are associated with worsened overall survival in MPN patients who undergo LT in univariate (P = .03; HR, 2.77; 95% CI, 1.10-7.00) and multivariate analysis (P < .05; HR, 2.11; 95% CI, 1.01-4.42). These data suggest that SRSF2 mutations contribute to the pathogenesis of LT and may guide novel therapeutic approaches for MPN patients who undergo LT.Keywords
This publication has 24 references indexed in Scilit:
- Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromesNature Genetics, 2011
- SomaticSF3B1Mutation in Myelodysplasia with Ring SideroblastsNew England Journal of Medicine, 2011
- IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617FLeukemia, 2011
- DNMT3AMutations in Acute Myeloid LeukemiaNew England Journal of Medicine, 2010
- Genomic and Biological Characterization of Exon 4 KRAS Mutations in Human CancerCancer Research, 2010
- IDH1 and IDH2 Gene Mutations Identify Novel Molecular Subsets Within De Novo Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B StudyJournal of Clinical Oncology, 2010
- Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome–negative myeloproliferative neoplasmsBlood, 2010
- Somatic Mutations ofIDH1andIDH2in the Leukemic Transformation of Myeloproliferative NeoplasmsNew England Journal of Medicine, 2010
- Genetic Analysis of Transforming Events That Convert Chronic Myeloproliferative Neoplasms to LeukemiasCancer Research, 2010
- Myeloproliferative disordersBlood, 2008