Overexpression of ATP1B1 predicts an adverse prognosis in cytogenetically normal acute myeloid leukemia.
ATP1B1 encodes the Na,K-ATPase β subunit, a key regulator of the Na+ and K+ electrochemical gradients across the plasma membrane and an essential regulator of cellular activity. We used several microarray datasets to test the prognostic efficacy of ATP1B1 expression in cytogenetically normal acute myeloid leukemia (CN-AML). Within the primary cohort (n = 157), high ATP1B1 expression (ATP1B1(high)) was associated with shorter overall survival (OS) and event-free survival (EFS) (P = 0.0068, P = 0.0039, respectively). Similar results were also obtained in the European Leukemia Net (ELN) Intermediate-I genetic category (OS: P = 0.0035, EFS: P = 0.0007). Multivariable analyses confirmed ATP1B1(high) is an independent predictor of shorter OS (P = 0.042) and EFS (P = 0.035). Analysis of another CN-AML cohort confirmed that ATP1B1(high) is associated with shorter OS (P = 0.0046, n = 162). In addition, up-regulation of oncogenes/onco-microRNAs such as MYCN, CCND2, CDK6, KIT and miR-155, among others, was associated with ATP1B1(high), which may be indicative of ATP1B1's leukemogenicity. Our results may improve risk stratification and indicate new therapeutic targets for CN-AML.
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Jin-long
JL
Shi
Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China.
Lin
L
Fu
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Qing
Q
Ang
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Guo-jing
GJ
Wang
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Jun
J
Zhu
Medical Engineering Support Center, Chinese PLA General Hospital, Beijing, China.
Wei-dong
WD
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012307:Risk Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
C503551:ATP1B1 protein, human; D014408:Biomarkers, Tumor; D000254:Sodium-Potassium-Exchanging ATPase
ATP1B1; CN-AML; expression; prognosis