Premium
Hypermethylation of ITGBL1 is associated with poor prognosis in acute myeloid leukemia
Author(s) -
Lian XinYue,
Ma JiChun,
Zhou JingDong,
Zhang TingJuan,
Wu DeHong,
Deng ZhaoQun,
Zhang ZhiHui,
Li XiXi,
He PinFang,
Yan Yang,
Lin Jiang,
Qian Jun
Publication year - 2019
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.27629
Subject(s) - myeloid leukemia , methylation , medicine , dna methylation , bisulfite sequencing , leukemia , acute promyelocytic leukemia , bone marrow , gastroenterology , oncology , cohort , polymerase chain reaction , biology , gene expression , cell culture , gene , biochemistry , retinoic acid , genetics
The current study was aimed to investigate integrin beta‐like 1 (ITGBL1) methylation pattern and its clinical relevance in patients with acute myeloid leukemia (AML). Real‐time methylation‐specific polymerase chain reaction (PCR; RQ‐MSP) and bisulfite sequencing PCR (BSP) were performed to detect the methylation of ITGBL1 promoter. Real‐time quantitative PCR (RT‐qPCR) was performed to analyze ITGBL1 transcript level. The results showed that ITGBL1 methylation level in 131 patients with AML was significantly higher than 29 controls ( p < 0.001). The ITGBL1‐hypermethylated group tended to have a higher bone marrow (BM) blasts ( p = 0.076). Meanwhile, ITGBL1‐hypermethylated patients tended to have a lower complete remission (CR) rate ( p = 0.102). ITGBL1‐hypermethylated patients had significantly shorter overall survival (OS) and leukemia‐free survival (LFS) than ITGBL1 hypomethylated patients in whole AML cohort ( p = 0.009 and 0.043, respectively) and patients with nonacute promyelocytic leukemia (APL ; p = 0.023 and 0.039, respectively). Multivariate analysis confirmed that the ITGBL1 methylation served as an independent prognostic factor in both patients with whole‐cohort AML ( p = 0.030) and patients with non‐APL ( p = 0.020). Furthermore, the ITGBL1 methylation level was significantly decreased in follow‐up AML patients who achieved complete remission after induction therapy ( P = 0.001). ITGBL1 methylation negatively correlated with ITGBL1 expression in patients with AML ( R = −0.328, p = 0.008). Moreover, demethylation of ITGBL1 could increase the ITGBL1 expression in the K562 leukemic cell line ( p < 0.05). In conclusion, the ITGBL1 hypermethylation is a potential biomarker for predicting prognosis and monitoring disease status in patients with AML.