ReviewTumor necrosis factor α in the onset and progression of leukemia

•Tumor necrosis factor α (TNF-α)-positive leukemia stem cells and leukemia cells correlate with adverse clinical parameters.•Two forms of TNF-α play different roles in leukemia.•TNF-α promotes leukemia stem cell expansion, but inhibits normal hematopoiesis.•TNF-α promotes formation of a tumor microenvironment.•Targeting of transmembrane TNF-α by monoclonal antibody eradicates leukemia stem cells and leukemia cells.

Tumor necrosis factor alpha (TNF-α), originally described as an anti-neoplastic cytokine, has been found, in apparent contradiction to its name, to play an important role in promoting the development and progression of malignant disease. Targeting TNF-α with TNF antagonists has elicited an objective response in certain solid tumors in phase I and II clinical trials. This review focuses on the relationship of TNF-α expressed by leukemia cells and adverse clinical features of leukemia. TNF-α is involved in all steps of leukemogenesis, including cellular transformation, proliferation, angiogenesis, and extramedullary infiltration. TNF-α is also an important factor in the tumor microenvironment and assists leukemia cells in immune evasion, survival, and resistance to chemotherapy. TNF-α may be a potent target for leukemia therapy.