MEIS inhibitors reduce the viability of primary leukemia cells and Stem cells by inducing apoptosis

Abstract

Leukemia stem cells (LSCs) exhibit self-renewal, resistance to standard treatments, and involvement in leukemia relapse. Higher Myeloid Ecotropic Integration Site-1 (MEIS1) expression in leukemic blast samples has been linked to resistance to conventional treatment. We studied the MEIS1 and associated factors in relapsed LSCs and assessed the effect of recently developed MEIS inhibitors (MEISi). Meis1 gene expression was found to be higher in patients with leukemia and relapsed samples. The majority of CD123+ and CD34+ LSCs demonstrated higher MEIS1/2/3 content. Depending on the patient chemotherapy regimen, Meis1 expression increased in relapsed samples. Although there are increased Meis2, Meis3, Hoxa9, Pbx1, or CD34 expressions in the relapsed patients, they are not correlated with Meis1 content in every patient or regimen. MEISi has reduced MEIS1 transcriptional activity and LSC cell survival by apoptosis. Pharmacological targeting with MEISi in LSCs could have a potential effect in limiting leukemia relapse and chemotherapeutic resistance.

Keywords: Acute leukemia; LSCs; MEIS inhibitor; Meis1.