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. 2021 Sep 23;22(19):10216.
doi: 10.3390/ijms221910216.

MiR-125a-3p and MiR-320b Differentially Expressed in Patients with Chronic Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation and Imatinib Mesylate

Juliana R B Martins  1 , Leonardo N Moraes  2 , Sarah S Cury  3 , Juliana Capannacci  1 , Robson Francisco Carvalho  3 , Célia Regina Nogueira  1 , Newton Key Hokama  1 , Paula O M Hokama  1
Affiliations

MiR-125a-3p and MiR-320b Differentially Expressed in Patients with Chronic Myeloid Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation and Imatinib Mesylate

Juliana R B Martins et al. Int J Mol Sci. .

Abstract

Chronic myeloid leukemia (CML), a hematopoietic neoplasm arising from the fusion of BCR (breakpoint cluster region) gene on chromosome 22 to the ABL (Abelson leukemia virus) gene on chromosome 9 (BCR-ABL1 oncogene), originates from a small population of leukemic stem cells with extensive capacity for self-renewal and an inflammatory microenvironment. Currently, CML treatment is based on tyrosine kinase inhibitors (TKIs). However, allogeneic hematopoietic stem cell transplantation (HSCT-allo) is currently the only effective treatment of CML. The difficulty of finding a compatible donor and high rates of morbidity and mortality limit transplantation treatment. Despite the safety and efficacy of TKIs, patients can develop resistance. Thus, microRNAs (miRNAs) play a prominent role as biomarkers and post-transcriptional regulators of gene expression. The aim of this study was to analyze the miRNA profile in CML patients who achieved cytogenetic remission after treatment with both HSCT-allo and TKI. Expression analyses of the 758 miRNAs were performed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Bioinformatics tools were used for data analysis. We detected miRNA profiles using their possible target genes and target pathways. MiR-125a-3p stood out among the downregulated miRNAs, showing an interaction network with 52 target genes. MiR-320b was the only upregulated miRNA, with an interaction network of 26 genes. The results are expected to aid future studies of miRNAs, residual leukemic cells, and prognosis in CML.

Keywords: allogeneic hematopoietic stem cell transplantation; chronic myeloid leukemia; imatinib mesylate; miR-125a-3p; miR-320b; miRNAs.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Heatmap of the normalized expression values of microRNAs in allo-HSCT and imatinib mesylate groups.
Figure 2
Figure 2
Protein–protein interaction of upregulated miRNA target genes. Gene interaction was performed using STRING and Cytoscape tools. Genes are represented by yellow rectangles and lines represent protein–protein associations.
Figure 3
Figure 3
Protein–protein interaction of downregulated miRNAs target genes. Gene interaction was performed using STRING and Cytoscape tools. Genes are represented by green rectangles and lines represent protein–protein associations.
Figure 4
Figure 4
Main upregulated miRNA target genes (A). Main downregulated miRNA target genes (B).
Figure 5
Figure 5
Summary of methodology steps and main results.
See this image and copyright information in PMC

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