BMI1-Inhibitor PTC596 in Combination with MCL1 Inhibitor S63845 or MEK Inhibitor Trametinib in the Treatment of Acute Leukemia.

ABSTRACT:

Purpose

Prognosis for acute myeloid leukemia (AML) patients is poor, particularly in TP53 mutated AML, secondary, relapsed, and refractory AML, and in patients unfit for intensive treatment, thus highlighting an unmet need for novel therapeutic approaches. The combined use of compounds targeting the stem cell oncoprotein BMI1 and activating the tumor suppressor protein p53 may represent a promising novel treatment option for poor risk AML patients.

Experimental design

The BMI1 inhibitor PTC596, MCL1 inhibitor S63845, and MEK inhibitor trametinib, as well as the p53 activator APR-246 were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells. AML cells represented all major morphologic and molecular subtypes

SUBMITTER: Seipel K 

PROVIDER: S-EPMC7867282 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature