The mutational burden of therapy-related myeloid neoplasms is similar to primary myelodysplastic syndrome but has a distinctive distribution

Deepak Singhal, Li Yan Wee, Monika M. Kutyna, Rakchha Chhetri, Joel Geoghegan, Andreas W. Schreiber, Jinghua Feng, Paul P.S. Wang, Milena Babic, Wendy T. Parker, Smita Hiwase, Suzanne Edwards, Sarah Moore, Susan Branford, Teodora Kuzmanovic, Nimit Singhal, Raghu Gowda, Anna L. Brown, Peer Arts, Luen B. ToPeter G. Bardy, Ian D. Lewis, Richard J. D’Andrea, Jaroslaw P. Maciejewski, Hamish S. Scott, Christopher N. Hahn, Devendra Hiwase

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26 Citations (Scopus)

Abstract

Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n = 129) and primary myelodysplastic syndrome (P-MDS, n = 108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5 vs. 7%), while spliceosomal complex mutations were more common in P-MDS (56.5 vs. 25.6%). In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with “Very low” or “Low” Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetics, disease-modifying therapy, and NRAS mutation. Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.

Original languageEnglish
Pages (from-to)2842-2853
Number of pages12
JournalLeukemia
Volume33
Issue number12
DOIs
Publication statusPublished or Issued - 2019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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