TY - JOUR
T1 - Chronic Myelomonocytic Leukemia
T2 - a Genetic and Clinical Update
AU - McCullough, Kristen B.
AU - Patnaik, Mrinal M.
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder, characterized by peripheral blood monocytosis and overlapping features between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). Clonal cytogenetic changes are seen in up to 30 % patients, while approximately 90 % have detectable molecular abnormalities. Most patients are diagnosed in the seventh decade of life. Gene mutations in ten-eleven translocation (TET) oncogene family member 2 (TET2) (60 %), SRSF2 (50 %), ASXL1 (40 %), and RAS (20-30 %) are frequent, with only frame shift and nonsense ASXL1 mutations negatively impacting overall survival. With the lack of formal guidelines, management and response criteria are often extrapolated from MDS and MPN. Contemporary molecularly integrated CMML-specific prognostic models include the Groupe Francais des Myelodysplasies (GFM) model and the Molecular Mayo Model, both incorporating ASXL1 mutational status. Hypomethylating agents and allogeneic stem cell transplant remain the two most commonly used treatment strategies, with suboptimal results. Clinical trials exploiting epigenetic and signal pathway abnormalities, frequent in CMML, offer hope and promise.
AB - Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder, characterized by peripheral blood monocytosis and overlapping features between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). Clonal cytogenetic changes are seen in up to 30 % patients, while approximately 90 % have detectable molecular abnormalities. Most patients are diagnosed in the seventh decade of life. Gene mutations in ten-eleven translocation (TET) oncogene family member 2 (TET2) (60 %), SRSF2 (50 %), ASXL1 (40 %), and RAS (20-30 %) are frequent, with only frame shift and nonsense ASXL1 mutations negatively impacting overall survival. With the lack of formal guidelines, management and response criteria are often extrapolated from MDS and MPN. Contemporary molecularly integrated CMML-specific prognostic models include the Groupe Francais des Myelodysplasies (GFM) model and the Molecular Mayo Model, both incorporating ASXL1 mutational status. Hypomethylating agents and allogeneic stem cell transplant remain the two most commonly used treatment strategies, with suboptimal results. Clinical trials exploiting epigenetic and signal pathway abnormalities, frequent in CMML, offer hope and promise.
KW - ASXL1
KW - CMML
KW - Hypomethylating agents
KW - Prognosis
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U2 - 10.1007/s11899-015-0271-4
DO - 10.1007/s11899-015-0271-4
M3 - Review article
C2 - 26122388
AN - SCOPUS:84941736530
SN - 1558-8211
VL - 10
SP - 292
EP - 302
JO - Current Hematologic Malignancy Reports
JF - Current Hematologic Malignancy Reports
IS - 3
ER -