Hypoxia-inducible factor (HIF) is the central master regulator of adaptation to decreased oxygen availability in both physiological and pathological conditions. In leukemia, HIF regulates tumor cell metabolic regulation, metastasis, and other tumor-adaptive survival. However, the regulatory role of HIF in different types of leukemia, including myeloid leukemia, has been unclear. In this chapter, the focus throughout is on the aspects of roles of HIF in the tumor mitochondria metabolic change that are relevant to the assessment and treatment of myeloid leukemia. The connection of HIF with metabolic modification and anaerobic metabolism, along with epigenetic modification, contribute to abnormal biological and clinical behavior of myeloid leukemia, including response to treatment. We have also explored the metabolic requirements of tumor cell proliferation in an attempt to understand why tumor cells escape hypoxia-induced cell growth inhibition. We believe that a better understanding of the mechanistic links between HIF-regulated cellular metabolism, growth control, and epigenetic modifications could be useful for the indication of pharmaceutical agents in myeloid leukemia.
Part of the book: Myeloid Leukemia