TY - JOUR
T1 - Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia
AU - Patnaik, M. M.
AU - Tefferi, A.
PY - 2016/2/5
Y1 - 2016/2/5
N2 - 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 Francąis des Myelodysplasies 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.
AB - 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 Francąis des Myelodysplasies 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.
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U2 - 10.1038/bcj.2016.5
DO - 10.1038/bcj.2016.5
M3 - Review article
C2 - 26849014
AN - SCOPUS:84957561306
SN - 2044-5385
VL - 6
JO - Blood cancer journal
JF - Blood cancer journal
M1 - e393
ER -