Oncotarget

Research Papers:

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

Jin-long Shi _, Lin Fu and Wei-dong Wang

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Oncotarget. 2015; 6:5299-5309. https://doi.org/10.18632/oncotarget.3024

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Abstract

Jin-long Shi1,*, Lin Fu2,*, Wei-dong Wang1

1Medical Engineering Support Center, Chinese PLA General Hospital, Beijing 100853, China

2Department of Hematology and Lymphoma Research Center, Peking University, Beijing 100191, China

*These authors have contributed equally to this work

Correspondence to:

Wei-dong Wang, e-mail: wangwd301@126.com

Keywords: ITPR2, expression, prognostic biomarker, cytogenetically normal acute myeloid leukemia

Received: December 02, 2014     Accepted: December 31, 2014     Published: March 12, 2015

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.


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