Nucleophosmin mutations in de novo acute myeloid leukemia: the age-dependent incidences and the stability during disease evolution.
Nucleophosmin (NPM) mutations have been found in a significant proportion of adults with de novo acute myeloid leukemia (AML), especially in those of a normal karyotype. These results provide a basis for studies of the pathogenesis in this specific subgroup of AML. In this study, NPM mutations were analyzed in 173 Chinese patients of de novo AML, including adults and children. We found that NPM mutations were present in 19.1% of the overall population and 40.3% of those with a normal karyotype. Adults had a significantly higher incidence of NPM mutations than children [32 of 126 (25.4%) versus 1 of 47 (2.1%), P < 0.001]. NPM mutations were closely associated with normal karyotype (P < 0.001) and internal tandem duplication of FLT3 (P = 0.002), but negatively associated with CEBPA mutations (P = 0.032) and expression of CD34 (P < 0.001) and HLA-DR (P = 0.003). Serial analyses of NPM mutations showed the mutation disappeared at complete remission, but the same mutation reappeared at relapse, except for one who lost the mutation at the second relapse, when new cytogenetic abnormalities emerged. None acquired novel mutations during the follow-up period. In conclusion, NPM mutations occur in an age-dependent fashion. Moreover, the findings that NPM mutations are stable during disease evolution and closely associated with disease status make it a potential marker for monitoring minimal residual disease.
Chou
Wen-Chien
WC
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Tang
Jih-Luh
JL
Lin
Liang-In
LI
Yao
Ming
M
Tsay
Woei
W
Chen
Chien-Yuan
CY
Wu
Shang-Ju
SJ
Huang
Chi-Fei
CF
Chiou
Rong-Jing
RJ
Tseng
Mei-Hsuan
MH
Lin
Dong-Tsamn
DT
Lin
Kai-Hsin
KH
Chen
Yao-Chang
YC
Tien
Hwei-Fang
HF
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005091:Exons; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin