Clinical significance of BECLIN1 and ATG5 expression in acute myeloid leukemia patients

Int J Clin Exp Pathol. 2018 Mar 1;11(3):1529-1537. eCollection 2018.

Abstract

Introduction: In acute myeloid leukemia (AML), it has been found that harnessing the autophagy process has led to leukemia cell death and had synergistic effects with chemotherapy. BECLIN1 and ATG5 are vital upstream regulators in the macroautophagy signaling pathway. Therefore, we explored the expression levels of BECLIN1 and ATG5 in AML patients and investigated their prognostic value, that of other clinical features.

Methods: Real-time quantitative PCR was used to investigate the mRNA levels of BECLIN1 and ATG5 in 101 newly diagnosed leukemia patients.

Results: AML samples with CEBPα or c-KIT mutations showed lower BECLIN1 expression levels compared with those without mutations (P=0.044 and P=0.036) and those with the c-KIT mutation showed lower ATG5 expression (P=0.040). Overexpression of BECLIN1 and ATG5 was related to a shorter overall survival (OS; P=0.02 and P=0.035) but not to disease-freesurvival (DFS). In multivariate analysis, the clinical characteristics exhibited no statistically significant differences in OS, except for the FLT3-ITD mutation (P=0.001) and age of the patients (P=0.032).

Conclusion: Our results indicate that high levels of BECLIN1 and ATG5 are associated with poor disease outcome. However, they are not independent risk factors for AML and further studies are needed to verify the underlying mechanism.

Keywords: ATG5; Acute myeloid leukemia; BECLIN1; autophagy; mRNA level; real-time quantitative PCR.