Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome Journal Article


Authors: Zhang, S. J.; Rampal, R.; Manshouri, T.; Patel, J.; Mensah, N.; Kayserian, A.; Hricik, T.; Heguy, A.; Hedvat, C.; Gonen, M.; Kantarjian, H.; Levine, R. L.; Abdel-Wahab, O.; Verstovsek, S.
Article Title: Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome
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. © 2012 by The American Society of Hematology.
Journal Title: Blood
Volume: 119
Issue: 19
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2012-05-10
Start Page: 4480
End Page: 4485
Language: English
DOI: 10.1182/blood-2011-11-390252
PROVIDER: scopus
PMCID: PMC3362363
PUBMED: 22431577
DOI/URL:
Notes: --- - "Export Date: 4 June 2012" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Adriana Heguy
    85 Heguy
  2. Cyrus Hedvat
    123 Hedvat
  3. Mithat Gonen
    716 Gonen
  4. Raajit Kumar Rampal
    139 Rampal
  5. Ross Levine
    490 Levine
  6. Su-Jiang Zhang
    4 Zhang
  7. Jay Prakash Patel
    53 Patel
  8. Todd Raymond Hricik
    26 Hricik
  9. Nana Yaa Takyiwaa Mensah
    7 Mensah