Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A

被引：250

作者：

Jankowska, Anna M. ^{[1
]}

Makishima, Hideki ^{[1
]}

Tiu, Ramon V. ^{[1
,2
]}

Szpurka, Hadrian ^{[1
]}

Huang, Yun ^{[3
]}

Traina, Fabiola ^{[1
]}

Visconte, Valeria ^{[1
]}

Sugimoto, Yuka ^{[1
]}

Prince, Courtney ^{[1
]}

O'Keefe, Christine ^{[1
]}

Hsi, Eric D. ^{[4
]}

List, Alan ^{[5
]}

Sekeres, Mikkael A. ^{[2
]}

Rao, Anjana ^{[3
]}

McDevitt, Michael A. ^{[6
]}

Maciejewski, Jaroslaw P. ^{[1
,2
]}

机构：

[1] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44106 USA

[2] Cleveland Clin, Dept Hematol Oncol & Blood Disorders, Leukemia Program, Cleveland, OH 44106 USA

[3] La Jolla Inst Allergy & Immunol, San Diego, CA USA

[4] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA

[5] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA

[6] Johns Hopkins Univ, Sch Med, Div Hematol & Hematol Malignancy, Baltimore, MD USA

来源：

BLOOD | 2011年 / 118卷 / 14期

关键词：

WORLD-HEALTH-ORGANIZATION; HISTONE METHYLTRANSFERASE; FREQUENT ALTERATIONS; UNIPARENTAL DISOMY; SOMATIC MUTATIONS; IDH2; MUTATIONS; TET2; GENE; CLASSIFICATION; REVEALS; H3K27;

D O I：

10.1182/blood-2010-10-311019

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (Blood. 2011;118(14):3932-3941)

引用

页码：3932 / 3941

页数：10

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