Mitochondrial dependency in progression of acute myeloid leukemia

• Acute Myeloid Leukemia (AML) initiation, progression and maintenance have a mitochondrial dependency.
• AML disease progression is dependent on mitochondrial oxidative phosphorylation and other mitochondrial metabolic pathways.
• There is an interconnection between mitochondria regulated metabolism, cellular stress response pathways and AML.
• Pharmacologically targeting various mitochondrial pathways help eradicating AML cells.
• Mitochondrial pathways can be targeted for differentiation therapy to treat AML.

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.