TY - JOUR
T1 - Clinical features of de Novo acute myeloid leukemia with concurrent DNMT3A, FLT3 and NPM1 mutations
AU - Loghavi, Sanam
AU - Zuo, Zhuang
AU - Ravandi, Farhad
AU - Kantarjian, Hagop M.
AU - Bueso-Ramos, Carlos
AU - Zhang, Liping
AU - Singh, Rajesh R.
AU - Patel, Keyur P.
AU - Medeiros, L. Jeffrey
AU - Stingo, Francesco
AU - Routbort, Mark
AU - Cortes, Jorge
AU - Luthra, Rajyalakshmi
AU - Khoury, Joseph D.
N1 - Funding Information:
The authors thank Sherry Pierce for assistance with data acquisition. This work was supported in part by the MD Anderson Cancer Center Support Grant (CA016672) from the National Cancer Institute.
Publisher Copyright:
© 2014 Loghavi et al.; licensee BioMed Central Ltd.
PY - 2014/10/4
Y1 - 2014/10/4
N2 - Background: De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AMLDNMT3A/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 AMLDNMT3A/FLT3/NPM1 patients.Results: Patients with AMLDNMT3A/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 < 0.001) and normal cytogenetics (p = 0.024) in comparison to patients within other mutation groups in this study. Among patients <60 years old, those with AMLDNMT3A/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 AMLDNMT3A/NPM1 had a significantly shorter OS compared to those with AMLFLT3-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.
AB - Background: De novo acute myeloid leukemia (AML) with concurrent DNMT3A, FLT3 and NPM1 mutations (AMLDNMT3A/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 AMLDNMT3A/FLT3/NPM1 patients.Results: Patients with AMLDNMT3A/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 < 0.001) and normal cytogenetics (p = 0.024) in comparison to patients within other mutation groups in this study. Among patients <60 years old, those with AMLDNMT3A/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 AMLDNMT3A/NPM1 had a significantly shorter OS compared to those with AMLFLT3-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.
KW - Acute myeloid leukemia
KW - DNMT3A
KW - FLT3
KW - NPM1
KW - Next-generation sequencing
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U2 - 10.1186/s13045-014-0074-4
DO - 10.1186/s13045-014-0074-4
M3 - Article
C2 - 25281355
AN - SCOPUS:84907942640
SN - 1756-8722
VL - 7
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 74
ER -
