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.
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.
Koh
Youngil
Y
Department of Internal Medicine, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea.
Park
Juwon
J
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Bae
Eun-Kyung
EK
Department of Biomedical Science, Hanyang University College of Medicine, Seoul, Republic of Korea.
Ahn
Kwang-Sung
KS
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kim
Inho
I
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.
Bang
Soo-Mee
SM
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Lee
Jae-Hoon
JH
Department of Internal Medicine, Gachon University College of Medicine Gil Hospital, Incheon, Republic of Korea.
Yoon
Sung-Soo
SS
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.
Lee
Dong Soon
DS
Department of Clinical Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
Lee
Young Yiul
YY
Department of Internal Medicine, Hanyang University Hospital, Seoul, Republic of Korea.
Park
Seonyang
S
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.
Kim
Byoung Kook
BK
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.
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
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin