NLRP3 participates in the differentiation and apoptosis of PMA‑treated leukemia cells.

Abstract

Acute myeloid leukemia (AML) is a clonal malignant proliferative disease. In recent years, with the use of all‑trans retinoic acid to induce cancer cell differentiation in acute promyelocytic leukemia, and its advantages of high efficacy and low toxic side effects, tumor differentiation therapy has become a research hotspot; however, the mechanisms underlying its role remain to be fully established. Nod‑like receptor family pyridine domain containing 3 (NLRP3) is the most extensively studied and well‑characterized inflammasome, is involved in a variety of inflammation‑related diseases, including cancer, and is a very attractive potential target for the study of novel therapeutic agents. Activation of the NLRP3 inflammasome is a double‑edged sword in tumor therapy, with evidence of protective anti‑tumor and pro‑tumor effects in different types of cancer. Whether the NLRP3 inflammasome promotes disease progression or exerts a protective anti‑tumor effect in hematological malignancies remains contested. In the present study, the protective anti‑tumor effects of NLRP3 on leukemia cells during their differentiation and maturation were investigated. It was found that the upregulation of NLRP3 expression induced using Phorbol 12‑Myristate 13‑Acetate played a role in promoting the differentiation and maturation of leukemia cells into monocytes/macrophages, and it was directly involved in the apoptosis of leukemia cells and the differentiation and maturation of CD11b+ cells. These results provide novel theoretical evidence for exploring the mechanism of differentiation therapy in leukemia and improves our understanding of the role of NLRP3 in hematologic tumors.