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 - 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 -