Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Feb 5;6(2):e393.
doi: 10.1038/bcj.2016.5.

Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia

M M Patnaik  1 , A Tefferi  1
Affiliations
Review

Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia

M M Patnaik et al. Blood Cancer J. .

Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder associated with peripheral blood monocytosis and an inherent tendency to transform to acute myeloid leukemia. CMML has overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Clonal cytogenetic changes are seen in ~30%, whereas gene mutations are seen in >90% of patients. Common cytogenetic abnormalities include; trisomy 8, -Y, -7/del(7q), trisomy 21 and del(20q), with the Mayo-French risk stratification effectively risk stratifying patients based on cytogenetic abnormalities. Gene mutations frequently involve epigenetic regulators (TET2 ~60%), modulators of chromatin (ASXL1 ~40%), spliceosome components (SRSF2 ~50%), transcription factors (RUNX1 ~15%) and signal pathways (RAS ~30%, CBL ~15%). Of these, thus far, only nonsense and frameshift ASXL1 mutations have been shown to negatively impact overall survival. This has resulted in the development of contemporary, molecularly integrated (inclusive of ASXL1 mutations) CMML prognostic models, including Molecular Mayo Model and the Groupe Français des Myélodysplasies model. Better understanding of the prevalent genetic and epigenetic dysregulation has resulted in emerging targeted treatment options for some patients. The development of an integrated (cytogenetic and molecular) prognostic model along with CMML-specific response assessment criteria are much needed future goals.

PubMed Disclaimer

Figures

Figure 1
Figure 1
OS of 409 patients with WHO-defined CMML, stratified by the Mayo–French cytogenetic risk stratification system.
Figure 2
Figure 2
Spectrum of gene mutations seen in patients with CMML.
Figure 3
Figure 3
Mutational evolution and clonal hierarchy in patients with CMML.
Figure 4
Figure 4
Isocitrate dehydrogenase mutations in CMML.
Figure 5
Figure 5
ASXL1 and EZH2 mutations in CMML.
See this image and copyright information in PMC

References

    1. Swederlow S, Camp E, Harris NL, Jaffe ES, Stefano PA, Stein H, et al. (eds). WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer: Lyon, France, 2008.
    1. Patnaik MM, Parikh SA, Hanson CA, Tefferi A. Chronic myelomonocytic leukaemia: a concise clinical and pathophysiological review. Br J Haematol 2014; 165: 273–286. - PubMed
    1. Patnaik MM, Wassie EA, Lasho TL, Hanson CA, Ketterling R, Tefferi A. Blast transformation in chronic myelomonocytic leukemia: risk factors, genetic features, survival, and treatment outcome. Am J Hematol 2015; 90: 411–416. - PubMed
    1. Wassie EA, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA et al. Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study. Am J Hematol 2014; 89: 1111–1115. - PubMed
    1. Such E, Cervera J, Costa D, Sole F, Vallespi T, Luno E et al. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica 2011; 96: 375–383. - PMC - PubMed

Publication types

MeSH terms