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PMID: 22289493 Published · ppublish English Journal Article Review

Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions.

Seminars in oncology ·Vol. 39 ·No. 1 ·2012-02-00 ·Pages 67-73

Muramatsu H, Makishima H, Maciejewski JP

Abstract

Chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML) are distinct, yet related, entities of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) characterized by morphologic dysplasia with accumulation of monocytes or neutrophils, respectively. Our understanding of the molecular pathogenesis of CMML and aCML has advanced, mainly due to the application of novel technologies such as array-based karyotyping and next-generation sequencing. In addition to previously known recurrent aberrations, somatic uniparental disomy affecting chromosomes 3, 4, 7, and 11 frequently occurs in CMML. Novel somatic mutations of genes, including those associated with proliferation signaling (CBL, RAS, RUNX1, JAK2 (V617F)) and with modification of epigenetic status (TET2, ASXL1, UTX, EZH2) have been found. Various combinations of mutations suggest a multistep pathogenesis and may account for clinical heterogeneity. Most recently, several spliceosome-associated-gene mutations were reported and SRSF2 mutations are frequently detected in CMML. The prognostic and diagnostic significance of these molecular lesions, in particular their value as biomarkers of response or resistance to specific therapies, while uncertain now is likely to be clarified as large systematic studies come to completion.

MeSH Terms
Humans Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/genetics,pathology Leukemia, Myelomonocytic, Chronic/genetics,pathology Prognosis
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Muramatsu Hideki
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Makishima Hideki
Maciejewski Jaroslaw P
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Article Info
Journal
Seminars in oncology
Abbr.
Semin Oncol
ISSN
1532-8708
DOI
10.1053/j.seminoncol.2011.11.004
Published
2012-02-00
Pages
67-73
Language
English
Region
United States
NLM ID
0420432
PMCID
PMC3523950
Subset
IM
Grants
NHLBI NIH HHS · K24 HL077522 · United States
NHLBI NIH HHS · R01 HL098511 · United States
External Links
PubMed source DOI: 10.1053/j.seminoncol.2011.11.004 PMC Full Text View journal details
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