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Methylation‐independent ITGA2 overexpression is associated with poor prognosis in de novo acute myeloid leukemia
Author(s) -
Lian XinYue,
Zhang Wei,
Wu DeHong,
Ma JiChun,
Zhou JingDong,
Zhang ZhiHui,
Wen XiangMei,
Xu ZiJun,
Lin Jiang,
Qian Jun
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26866
Subject(s) - myeloid leukemia , methylation , leukemia , bisulfite sequencing , medicine , acute promyelocytic leukemia , cancer research , polymerase chain reaction , myeloid , real time polymerase chain reaction , immunology , dna methylation , oncology , biology , gene expression , cell culture , gene , retinoic acid , genetics
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.