title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Koh
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Juwon
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Bae
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kwang-Sung
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Soo-Mee
authors.initials: SM
authors.lastname: Bang
authors.affiliation: Department of Internal Medicine, Gachon University College of Medicine Gil Hospital, Incheon, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea. ssysmc@snu.ac.kr.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. ssysmc@snu.ac.kr.|Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. ssysmc@snu.ac.kr.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Hanyang University Hospital, Seoul, Republic of Korea.
authors.forename: Young Yiul
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Seonyang
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Byoung Kook
authors.initials: BK
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin