Non-A type nucleophosmin 1 gene mutation predicts poor clinical outcome in de novo adult acute myeloid leukemia: differential clinical importance of NPM1 mutation according to subtype

• Published in: International journal of hematology Vol. 90; no. 1; pp. 1 - 5
• Main Authors: Koh, Youngil, Park, Juwon, Bae, Eun-Kyung, Ahn, Kwang-Sung, Kim, Inho, Bang, Soo-Mee, Lee, Jae-Hoon, Yoon, Sung-Soo, Lee, Dong Soon, Lee, Young Yiul, Park, Seonyang, Kim, Byoung Kook
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.07.2009; Springer; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Clinical outcomes; Disease-Free Survival; Female; Hematologic and hematopoietic diseases; Hematology; Humans; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Mutation; Nuclear Proteins - genetics; Oncology; Rapid Communication; Retrospective Studies; Survival Rate; AML; NPM1; Prognosis; Human; Acute myelogenous leukemia; Hematology; NPM1 gene; Malignant hemopathy; De novo; Adult; Genetics; Mutation; Predictive factor; Subtype; Cancer
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-009-0350-1

Mutations of nucleophosmin gene (NPM1) are known to be related to good prognosis in AML patients lacking FLT3 internal tandem duplication (FLT3-ITD). Recently, NPM1 mutations other than type A were reported, but their clinical significance is not well known. Retrospective medical record review of 106 de novo AML patients lacking FLT3-ITD, who received induction chemotherapy from three centers in Korea between 1997 and 2007, was performed. Direct sequencing of NPM1 and RT-PCR for FLT3-ITD was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for detection of mutations. NPM1 mutation was detected in 18 patients, where 13 were type A mutants and 5 were non-type A mutants. CR, CR1-D and OS was not different according to NPM1 mutational status overall. But, non-type A NPM1 mutation was related to shorter CR1-D when compared with NPM1 wild types and NPM1 type A mutation ( p = 0.004). OS was shorter in non-type A mutants when compared with NPM1 wild-type patients and NPM1 type A mutants ( p = 0.001). The type of mutation of NPM1 is important for prognosis in de novo AML lacking FLT3-ITD. Non-A type NPM1 mutation is a poor prognostic factor.