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

The study of 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 study showed that human leukemia cells THP-1, HL-60, and K562 increased their resistance to TRAIL-induced death in vitro as a result of induction of myeloid differentiation in them by exogenous factors in all directions of myelopoiesis, except for erythroid, by reducing the expression of DR4 and DR5 receptors on the cell surface. It was also found that ONC 201, tunicamycin, and SAHA (hydroxamic acid suberoylanilide), capable of causing an increase in the expression of DR5 in leukemic 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 revealed that human leukemia cells THP-1, HL-60, and K562 developed resistance to TRAIL-induced death in vitro due to myeloid differentiation induced by exogenous factors, which led to reduced expression of DR4 and DR5 receptors on cell surface. Furthermore, substances such as ONC 201, tunicamycin, and SAHA, which can increase DR5 expression in leukemic cells, were found to suppress TRAIL resistance induced by differentiation factors. These findings are significant for the development of drugs and strategies to improve the treatment of myeloid leukemia.