Evaluation of miR-125b expression pattern and its alteration following AS2O3 treatment in Acute Promyelocytic Leukemia(APL) patients

Introduction: miR-125b is a potential oncomiR and currently believed to play important roles in the pathogenesis of human leukemia. Aim: To investigate the expression profile of miR-125b in APL patients at diagnosis, and to evaluate whether treatment with AS2O3 changes its expression pattern. Methods : We evaluated the expression of miR-125b in 36(30 new diagnosed and 6 relapsed) adult APL using quantitative real-time polymerase chain reaction. Additionally, we examined 15 paired samples collected before and 28 days after the treatment to seek alterations in the expression of mir- 125b after AS2O3 treatment. Results: We found very high expression of miR-125b in newly diagnosed APL patients compared to that in mononuclear bone marrow cells from healthy donors, values ranged from 112 to 19000 fold (mean, 5000-fold). Also the expression level of miR-125b was higher in newly diagnosed patients than those in relapsed samples, values ranged from 5 to 2272 fold (mean, 472-fold). 28 days after treatment whilepatients had individual difference in alteration of PML/RARA expression, miR-125b expression decreased significantly in all patients independent of biological differencebetween patients but also was higher than that of normal control, values ranged from 6 to 455 fold (mean, 215-fold). No correlations were found between RQ values andpatients sex, age, WBC count, PML/RARA isoform and FLT3 mutations status. Conclusion: miR-125b expression may provide a novel molecular marker in addition to PML/RARA for monitoring the response to treatment and minimal residual disease (MRD) and targeting therapy in APL patients. Further studies are required to investigate the prognostic importance of miR-125b expression in APL.

Evaluation of miR-125b expression pattern and its alteration following AS2O3 treatment in Acute Promyelocytic Leukemia(APL) patients Keywords:

PML/RARA , oncomiR , Arsenic