FLT3-ITD-associated gene-expression signatures in NPM1-mutated cytogenetically normal acute myeloid leukemia.
Concomitance of the FLT3-ITD mutation is associated with poor prognosis in NPM1-mutated cytogenetically normal acute myeloid leukemia (CN-AML) patients, and precise studies on its role in leukemogenesis are needed; these may be elucidated at the molecular level by gene express profiling. In the present study, we built a gene-expression-based classifier using prediction analysis of microarray to characterize the FLT3-ITD signature in NPM1-mutated CN-AML patients, which comprised 10 annotated genes, and demonstrated an overall accuracy of 83.8 % in cross-validation. To characterize the signature in another way, differential expression was revealed for 34 genes by class comparison, and the up-regulation of LAPTM4B and MIR155HG was validated by quantitative RT-PCR in our small cohort of NPM1-mutated CN-AML samples, which appeared to be associated with this specific subtype. The 10-gene classifier and differentially expressed genes identified in this study indicate a potential utility for risk-assessed treatment stratification, and suggest new therapeutic targets for these high-risk AML patients.
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China.
Liang
L
Huang
Kuangguo
K
Zhou
Yunfan
Y
Yang
Zhen
Z
Shang
Jue
J
Wang
Di
D
Wang
Na
N
Wang
Danmei
D
Xu
Jianfeng
J
Zhou
D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020440:Gene Duplication; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D015203:Reproducibility of Results; D020080:Tandem Repeat Sequences; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3