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

Authors
  • PINTO, CAMILA ALBUQUERQUE1
  • DE SOUSA PORTILHO, ADRHYANN JULLYANNE2
  • BARBOSA, MARITZA CAVALCANTE3
  • DE MORAES, MARIA ELISABETE AMARAL2
  • DE LEMOS, JOSÉ ALEXANDRE RODRIGUES4
  • BURBANO, ROMMEL MΑRIO RODRIGUEZ1
  • MOREIRA-NUNES, CAROLINE AQUINO2
  • 1 Human Cytogenetics Laboratory, Biological Science Institute, Federal University of Pará, Belém, Brazil
  • 2 Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil
  • 3 Faculty of Pharmacy, Federal University of Ceará, Fortaleza, Brazil
  • 4 Biological Science Institute, Federal University of Pará, Belém, Brazil
Type
Published Article
Journal
In Vivo
Publisher
International Institute of Anticancer Research
Publication Date
Sep 03, 2021
Volume
35
Issue
5
Pages
2661–2667
Identifiers
DOI: 10.21873/invivo.12549
PMID: 34410954
PMCID: PMC8408721
Source
PubMed Central
Keywords
Disciplines
  • Research Article
License
Unknown

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.

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