Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX,,EZH2,and DNMT3A

Anna M. Jankowska, Hideki Makishima, Ramon V. Tiu, Hadrian Szpurka, Yun Huang, Fabiola Traina, Valeria Visconte, Yuka Sugimoto, Courtney Prince, Christine O'Keefe, Eric D. Hsi, Alan List, Mikkael A. Sekeres, Anjana Rao, Michael A. McDevitt, Jaroslaw P. Maciejewski

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic myelomonocytic leukemia (CMML), a myelodysplastic/ myeloproliferative neoplasm, is characterized by monocytic proliferation, dysplasia, and progression to acute myeloid leukemia. CMML has been associated with somatic mutations in diverse recently identified genes. We analyzed 72 well-characterized patients with CMML (N ∇ 52) and CMML-derived acute myeloid leukemia (N ∇ 20) for recurrent chromosomal abnormalities with the use of routine cytogenetics and single nucleotide polymorphism arrays along with comprehensive mutational screening. Cytogenetic aberrations were present in 46% of cases, whereas single nucleotide polymorphism array increased the diagnostic yield to 60%. At least 1 mutation was found in 86% of all cases; novel UTX, DNMT3A, and EZH2 mutations were found in 8%, 10%, and 5.5% of patients, respectively. TET2 mutations were present in 49%, ASXL1 in 43%, CBL in 14%, IDH1/2 in 4%, KRAS in 7%, NRAS in 4%, and JAK2 V617F in 1% of patients. Various mutant genotype combinations were observed, indicating molecular heterogeneity in CMML. Our results suggest that molecular defects affecting distinct pathways can lead to similar clinical phenotypes.

Original languageEnglish (US)
Pages (from-to)3932-3941
Number of pages10
JournalBlood
Volume118
Issue number14
DOIs
StatePublished - Oct 6 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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