Metabolic Dysregulation in Normal and Malignant Hematopoiesis

Over the past decade, the metabolic alterations that occur during tumorigenesis have been recognized as a key feature required for the transformation and maintenance of malignant cells. In order to meet the demands of unrestrained growth, tumor cells must adopt metabolic phenotypes that provide sufficient energy generation, biosynthetic precursor molecules, maintenance of redox/oxidative stress balance and intracellular biochemical homeostasis for growth and survival. Many of these deregulated pathways may predispose premalignant cells to genomic instability resulting to aneuploidy. These phenotypes allow tumor cells to cease functioning as part of an integrated tissue, and evolve independently along a trajectory ultimately leading to malignant disease. During this process, cells must adapt to abnormal microenvironmental conditions that develop after tissue architecture and homeostatic regulation are disrupted. Based on recent work, we will provide an overview of the metabolic alterations, such as mutations in isocitrate dehydrogenase genes that occur in malignancies of the myeloid an lymphoid system. Although the importance of these metabolic alterations to specific disease states, including Acute Myeloid Leukemia and T cell lymphomas, remains to be determined, there may be opportunities for novel therapeutic intervention. Recent advances based on these molecular changes will be discussed.