Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia. Issue 12 (21st August 2018)

• Record Type: Journal Article
• Authors: Lian, Xin‐Yue; Zhang, Wei; Wu, De‐Hong; Ma, Ji‐Chun; Zhou, Jing‐Dong; Zhang, Zhi‐Hui; Wen, Xiang‐Mei; Xu, Zi‐Jun; Lin, Jiang; Qian, Jun
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 12(2018:Dec.)
• Page Start: 9584
• Page End: 9593
• Publication Date: 2018-08-21
• Subjects: acute myeloid leukemia -- expression -- ITGA2 -- methylation -- prognosis; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26866
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Previous studies have been indicated that integrin α2 (ITGA2) may be important in cell migration, invasion, survival, and angiogenesis. However, the correlation between ITGA2 expression and acute myeloid leukemia (AML) is still unclear. Real‐time quantitative polymerase chain reaction was carried out to analyze ITGA2 messenger RNA level. Methylation‐specific polymerase chain reaction (PCR) and bisulfite sequencing PCR were performed to detect the methylation of ITGA2 promoter. ITGA2 expression was significantly upregulated in 134 de novo AML patients compared with 33 controls ( p = 0.007). ITGA2 high group had markedly lower complete remission (CR) rate than ITGA2 low group ( p = 0.011). Furthermore, the overall survival in ITGA2 high patients was significantly shorter than ITGA2 low patients throughout AML cohort, non–acute promyelocytic leukemia (APL) and cytogenetic normal‐AML ( p = 0.001, 0.002, and 0.044, respectively). Multivariate analysis confirmed that ITGA2 overexpression served as an independent prognostic factor in both whole‐cohort AML patients ( p = 0.018) and non‐APL AML patients ( p = 0.021). Besides, ITGA2 expression level was significantly decreased in AML patients after CR ( p = 0.011), and was returned at the time of relapse phase ( p = 0.021). Moreover, unmethylated ITGA2 promoter was identified in normal controls, leukemia cell lines, and primary leukemia cells with low or high ITGA2 expression. In conclusions, methylation‐independent ITGA2 overexpression is associated with poor prognosis in AML. Abstract : Integrin α2 (ITGA2) expression was significantly upregulated in 134 de novo acute myeloid leukemia (AML) patients compared with 33 controls ( p = 0.007). Furthermore, the overall survival in high ITGA2 expression patients was significantly shorter than low ITGA2 expression patients throughout AML cohort, non–acute promyelocytic leukemia (APL), and cytogenetic normal‐AML ( p = 0.001, 0.002, and 0.044, respectively). Multivariate analysis confirmed that ITGA2 overexpression served as an independent prognostic factor in both whole‐cohort AML patients ( p = 0.018) and non‐APL AML patients ( p = 0.021).