Shedding light on new form of combination therapy in acute promyelocyte leukemia

Narjes Yazdi,1 Mohammad houshmand,2 Alireza kazemi,3 Mahin nikougoftar zarif,4,*

1. Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University
2. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine
3. Department Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Scienc
4. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine

Abstract

Introduction

Although physicians have taken a variety approaches for the treatment of acute promyelocytic leukemia (apl), there is not a prosperous treatment due to the relapse and drug resistance in patients. in this study, we decided to investigate the therapeutic effect of two combined drugs on hl-60 cells: 5-azacitidine (5-aza) as a dna methylation inhibitor which has a therapeutic application in leukemia and chloroquine (cq), an autophagy inhibitor, as a potential anticancer agent.

Methods

To elucidate the effect of aza and cq on hl-60 cell line, cells were exposed to aza (1 micromolar), cq (25 micromolar) and the combination of both drugs for 48 hours. q-real-time pcr was performed to measure bcl2, caspase-3, caspase-9, bax, bak and beclin1 mrna expression. the percentage of apoptotic cells was determined by flowcytometry using annexinv/pi apoptosis detection kit.

Results

The results demonstrated a remarkable down-regulation of bcl2 and beclin1 mrna expression besides up-regulation of caspase-3, caspase-9, bax, and bak in cells which treated with combined drugs in comparison to cells which treated with one of them. moreover, the treatment with both aza and cq demonstrated more apoptosis in hl-60 cells as opposed to aza or cq alone which may relate to autophagy pathway.

Conclusion

As a result, utilizing a combination of aza and cq may propose the important role of autophagy in the suppression of apl cells development.

Keywords

5-azacitidine, chloroquine, combination therapy, apl