Multidrug resistance phenotype and its relation to stem cell characteristics in chronic myeloid leukemia

Abstract

The present work aimed to evaluate the expression profile of genes related to stem cells (SC) characteristics during the acquisition of the multidrug resistance (MDR) phenotype in the chronic myeloid leukemia (CML). For this, the K562 (non MDR) and FEPS (MDR) cell lines were used. K562 cells had resistance induced by exposure to daunorubicin (DNR), and induction was confirmed by flow cytometry with an increase in ABCB1 expression in K562 cells treated at the highest concentration. Real-time PCR gene expression analysis showed a direct relationship in the expression of OCT4 and ABCB1 genes, with an increase in ABCB1 expression after exposure to DNR, followed by an increase in OCT4 gene expression. This direct relationship was confirmed in the MDR FEPS cells that had the ABCB1 gene silenced. For the ALOX5 gene, we observed an inverse relationship with ABCB1, with a decrease in the expression of ALOX5 in the DNR-transformed K562 cells, and an increase in the expression of this gene when ABCB1 was silenced in the FEPS cells. Thus, during the acquisition of the MDR phenotype by the K562 cells, it was possible to observe that there is an increase in the expression of ABCB1, accompanied by the expression of OCT4, while the expression of ALOX5 is decreased.