Endoplasmic reticulum stress and oxidative stress in acute myeloid leukemia

Abstract

Use of differentiation-inducing agents (all-trans retinoic acid and arsenic trioxide) that degradate fusion PML-RARα receptor have revolutionized management of acute promyelocytic (APL) leukemia in 2008. However, despite significant advances in the treatment of APL, the cure rates of patients suffering with other acute myeloid leukemia (AML) subtypes are still not satisfying. Abnormal reactive oxygen species levels and constitutive expression of ER stress marker proteins are characteristic of AML. AML patients with activated unfolded protein response and increased ER chaperone levels showed suppressed CEBPα protein expression. CEBPα is an essential transcription factor that regulates multiple aspects of myelopoiesis. Understanding how the unfolded protein response trigger down-regulation of CEBPα and lead to differentiation blockage opens new possibilities for the design of anti-AML therapeutic strategies.