Clinical features of De Novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations

Journal of Hematology & Oncology

Joseph D Khoury³  Rajyalakshmi Luthra³  Jorge Cortes¹  Mark Routbort³  Francesco Stingo²  L Jeffrey Medeiros³  Keyur P Patel³  Rajesh R Singh³  Liping Zhang³  Carlos Bueso-Ramos³  Hagop M Kantarjian¹  Farhad Ravandi¹  Zhuang Zuo³  Sanam Loghavi³ 

[1] Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0428, Houston 77030, TX, USA;Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1411, Houston 77030, TX, USA;From the Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0072, Houston 77030, TX, USA

关键词: NPM1;    FLT3;    DNMT3A;    Next-generation sequencing;    Acute myeloid leukemia;   

Others  :  1144223
DOI  :  10.1186/s13045-014-0074-4

 received in 2014-08-18, accepted in 2014-09-23,  发布年份 2014

【 摘 要 】

Background

De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AML^{DNMT3A/FLT3/NPM1}) has been suggested to represent a unique AML subset on the basis of integrative genomic analysis, but the clinical features of such patients have not been characterized systematically.

Methods

We assessed the features of patients (n?=?178) harboring mutations in DNMT3A, FLT3 and/or NPM1, including an index group of AML^{DNMT3A/FLT3/NPM1} patients.

Results

Patients with AML^{DNMT3A/FLT3/NPM1} (n?=?35) were significantly younger (median, 56.0 vs. 62.0 years; p?=?0.025), mostly women (65.7% vs. 46.9%; p?=?0.045), and presented with a higher percentage of bone marrow blasts (p?DNMT3A/FLT3/NPM1 had a shorter event-free survival (EFS) (p?=?0.047). DNMT3A mutations and not FLT3 or NPM1 mutations were independently associated with overall survival (OS) (p?=?0.026). Within mutation subgroups, patients with AML^DNMT3A/NPM1 had a significantly shorter OS compared to those with AML^{FLT3-ITD/NPM1} (p?=?0.047) suggesting that the adverse impact of DNMT3A mutations is more pronounced than that of FLT3-ITD among patients with NPM1 mutation.

Conclusions

DNMT3A has a significant dominant effect on the clinical features and outcomes of de novo AML patients with concurrent DNMT3A, FLT3 and NPM1 mutations.

【 授权许可】

   
2014 Loghavi et al.; licensee BioMed Central Ltd.

【 图 表 】

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