title: High expression of inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) as a novel biomarker for worse prognosis in cytogenetically normal acute myeloid leukemia.
abstract: Inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) is a key regulator for the activity of calcium ion transmembrane transportation, which plays a critical role in cell cycle and proliferation. However, the clinical impact of ITPR2 in cytogenetically normal acute myeloid leukemia (CN-AML) remained unknown. Several microarray datasets were used to evaluate the association between ITPR2 expression and clinical and molecular characteristics. ITPR2 showed a higher expression in CN-AML patients than normal persons. In a cohort of 157 CN-AML patients, high ITPR2 expression (ITPR2high) was associated with dramatically shorter overall survival (OS; P = 0.004) and event-free survival (EFS; P = 0.01), which were also shown in the European Leukemia Net (ELN) intermediate-I genetic category (OS: P = 0.0066; EFS: P = 0.009). Multivariable analyses adjusting for known prognostic factors confirmed ITPR2high to be associated with shorter OS (P = 0.0019) and EFS (P = 0.012). The prognostic value of ITPR2 was further validated in another cohort of 162 CN-AML patients (P = 0.007). In addition, first gene/microRNA expression signatures were derived that associated with ITPR2high on the genome-wide scale, which provided many indications to illustrate the possible mechanisms why ITPR2 could function. These results could aid to identify new targets and design novel therapeutic strategies for CN-AML patients.
authors.affiliation: Medical Engineering Support Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Jin-long
authors.initials: JL
authors.lastname: Shi
authors.affiliation: Department of Hematology and Lymphoma Research Center, Peking University, Beijing 100191, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Medical Engineering Support Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C506927:ITPR2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D035683:MicroRNAs
keywords: ITPR2; cytogenetically normal acute myeloid leukemia; expression; prognostic biomarker