“The role of autophagy in patients with acute leukemia”

Abstract

Acute leukemia is a malignant disease that affects a large proportion of the world population. It can be classified into AML and ALL. Different types and subtypes of acute leukemia require different treatments. Acute myeloid leukemia occurs mainly in the elderly whereas ALL occurs predominantly in children. Whilst 80% of children with ALL are cured, the outcomes for most AML patients remain poor and treatment strategies to improve this are needed. Autophagy plays an important role in both cell death and cell survival. It can either inhibit or promote tumorigenesis depending on the stage of the tumor and the stresses encountered. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. However, autophagy may also act as a pro-survival mechanism to protect cancer cells from various forms of cellular stresses. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as cell-fate decision machinery. Beclin-1 and MAP1LC3B are both key autophagy-promoting genes. Beclin-1, a key regulator of autophagy formation, has been considered as a haploinsufficient tumor suppressor. B-cell lymphoma-2, the first protein found to interact with beclin-1, was shown to possess an anti-autophagy function in addition to its well-established role in apoptosis inhibition. Because these anti-apoptotic proteins are usually over-expressed in cancer cells, the Bcl-2 protein may have an additive effect on oncogenic properties through inhibition of autophagy.