Myeloid Differentiation Increases Resistance of Leukemic Cells to TRAIL-Induced Death by Reducing the Expression of DR4 and DR5 Receptors

Studying the mechanisms of resistance of tumor cells to TRAIL-induced death remains an urgent task, since this cytokine is an important highly selective molecular effector of antitumor immunity. Our work has shown that human leukemia cells THP-1, HL-60, and K562, as a result of induction of myeloid differentiation in them by exogenous factors in vitro in all directions of myelopoiesis, except for erythroid, increase their resistance to TRAIL-induced death by reducing the expression of receptors DR4 and DR5 on the cell surface. It was also found that ONC201, tunicamycin, and SAHA (hydroxamic acid suberoylanilide), capable of inducing an increase in DR5 expression on leukemia cells, suppressed their TRAIL resistance induced by differentiation factors. The results obtained are of interest for the development of drugs and strategies to improve the effectiveness of the treatment of myeloid leukemia.

Automated summary

The study found that induction of myeloid differentiation in leukemia cells can increase their resistance to TRAIL-induced death, but certain substances can suppress this resistance and improve treatment effectiveness.