TY - JOUR
T1 - Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation
T2 - UTX,,EZH2,and DNMT3A
AU - Jankowska, Anna M.
AU - Makishima, Hideki
AU - Tiu, Ramon V.
AU - Szpurka, Hadrian
AU - Huang, Yun
AU - Traina, Fabiola
AU - Visconte, Valeria
AU - Sugimoto, Yuka
AU - Prince, Courtney
AU - O'Keefe, Christine
AU - Hsi, Eric D.
AU - List, Alan
AU - Sekeres, Mikkael A.
AU - Rao, Anjana
AU - McDevitt, Michael A.
AU - Maciejewski, Jaroslaw P.
PY - 2011/10/6
Y1 - 2011/10/6
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2010-10-311019
DO - 10.1182/blood-2010-10-311019
M3 - Article
C2 - 21828135
AN - SCOPUS:80053135096
SN - 0006-4971
VL - 118
SP - 3932
EP - 3941
JO - Blood
JF - Blood
IS - 14
ER -