Determination of MEIS1 (myeloid ecotrophic insertion site 1) expression profile in leukemia stem cells and investigation of the effect of MEIS1 inhibitors

Acute leukemia (AL) is a poor progressive resistant hematological disease, which has different subtypes and immunophenotypic properties according to leukemic blasts. AL is a disease caused by genetic changes and probably by Leukemia Stem Cells (LSCs), which determine its prognosis and endurance. LSCs are Hematopoietic Stem Cells (HSCs)-derived cells that underwent a malignant transformation. Even though the number of LSCs is low, they have the characteristics of self-renewal, resistance to chemotherapy, and relapse of leukemia. The MEIS1 (Myeloid Ecotropic Integration Site-1) protein is a member of the TALE (Three Amino Acids Loop Extension) family of Homeodomain (HD) proteins and can bind to DNA. Studies have proved that overexpression of MEIS1 protein can reason tumorigenesis of many cancers. Increased expression of MEIS1 protein has been determined in Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML) patients. Resistance to conventional chemotherapy was observed in samples with high MEIS1 expression. Small molecule inhibitors of the MEIS1 protein can be used to remove the effect of chemotherapy resistance on the leukemia and LSCs of the MEIS1 protein. This study, it is aimed to investigate MEIS1 proteins which are known to be effective in leukemia development and relapsed in LSCs, and to target MEIS activity with newly developed drug structured MEIS1Inhibitors (MEIS1i). In this study of BM-PB samples from patients with AML/ALL (n=65), we discovered that MEIS1i had a negative impact on MEIS protein activity, LSCs cell survival, and the apoptotic pathway. MEIS1i-1 and MEIS1i-2 inhibitors also reduced the levels of expression of known genes linked to cancer growth and survival in patient samples. In this study, we also discovered that MEIS1 gene expression plays a significant role in leukemia relapse and resistance to chemotherapy treatment. The findings in these studies will be the basis for future animal models and preclinical studies. Successful completion of these goals will enable leukemia to develop effective MEIS1i; thus, it will contribute to the development of an alternative drug for leukemia treatments.