Mitochondrial dependency in progression of acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a clonal hematopoietic malignant disorder which arises due to dysregulated differentiation, uncontrolled growth and inhibition of apoptosis leading to the accumulation of immature myeloid progenitor in the bone marrow. The heterogeneity of the disease at the molecular and cytogenetic level has led to the identification of several alteration of biological and clinical significance. One of the alterations which have gained attention in recent times is the altered energy and metabolic dependency of cancer originally proposed by Warburg. Mitochondria are important cell organelles regulating cellular energetic level, metabolism and apoptosis which in turn can affect cell proliferation and differentiation, the major manifestations of diseases like AML. In recent times the importance of mitochondrial generated ATP and mitochondrial localized metabolic pathways has been shown to play important role in the progression of AML. These studies have also demonstrated the clinical significance of mitochondrial targets for its effectiveness in combating relapsed or refractory AML. Here we review the importance of the mitochondrial dependency for the progression of AML and the emergence of the mitochondrial molecular targets which holds therapeutic importance.

Keywords: Acute myeloid leukemia; Altered metabolism; Cellular stress; Drug targets; Mitochondria; Oxidative phosphorylation.