Activation of the HIF-1 pathway in childhood ALL

Hypoxia-inducible factor-1 (HIF-1) is the key regulator of adaptive responses to reduced oxygen availability, including erythropoiesis, angiogenesis and energy metabolism. Recently we demonstrated by immunohistochemistry that the oxygen regulated component of HIF-1 (HIF-1α) is overexpressed in clusters of leukemic cells in bone marrow (BM) specimens of childhood acute lymphoblastic leukemia (ALL) and absent in biopsies of normal BM. Half the HIF-1α positive ALL biopsies exhibited coexpression with vascular endothelial growth factor (VEGF), an important pro-angiogenic HIF-1 target gene. Comparing the genomic resp…