Combined Therapy of ATRA and Imatinib Mesylate Decreases BCR-ABL and ABCB1/MDR1 Expression Through Cellular Differentiation in a Chronic Myeloid Leukemia Model.

Abstract

BACKGROUND/AIM:

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disease, and a major challenge for the eradication of CML is to understand the cause of the permanence of minimal residual disease (DRM). This work aimed to induce the maturation of leukemic stem cells with All-trans-retinoic acid (ATRA), making them sensitive to treatment with Imatinib (IM).

MATERIALS AND METHODS:

K562 cells were treated with IM and with the combined therapy of ATRA together with IM for 48 and 72 h. The expression of BCR-ABL gene and multidrug resistance gene ABCB1 were evaluated using RT-qPCR.

RESULTS:

The combined ATRA and IM therapy showed a discreet cell differentiation pattern, evidenced by the panoptic morphology analysis at 48 and 72 h of treatment. The BCR-ABL expression showed no statistical difference when treated alone with IM, however in combination with ATRA, the expression was statistically significant in 48 and 72 h (p≤0.0001) and when the treatment groups were compared to each other (p≤0.001). The ABCB1 gene expression showed a decrease in isolated IM therapy (p≤0.05) and in the combination in 48 and 72 h (p≤0.0001).

CONCLUSION:

Combined ATRA and IM therapy was shown to be effective in decreasing BCR-ABL and ABCB1 genes, possibly through the differentiation of blast cells, demonstrating that the therapy could be potentially effective in the blast crisis of the disease and for those patients who develop resistance to available CML treatments.

• Authors: Camila Albuquerque Pinto, Adrhyann Jullyanne DE Sousa Portilho, Maritza Cavalcante Barbosa, Maria Elisabete Amaral DE Moraes, José Alexandre Rodrigues DE Lemos, Rommel Mαrio Rodriguez Burbano, Caroline Aquino Moreira-Nunes
• Journal: In vivo (Athens, Greece) (In Vivo) 2021 Sep-Oct Vol. 35 Issue 5 Pg. 2661-2667 ISSN: 1791-7549 [Electronic] Greece
• PMID: 34410954 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Benzamides
• Piperazines
• Pyrimidines
• Tretinoin
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics)
• Apoptosis
• Benzamides
• Cell Differentiation
• Drug Resistance, Neoplasm (genetics)
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Imatinib Mesylate (pharmacology)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics)
• Piperazines
• Pyrimidines (pharmacology)
• Tretinoin