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,Newton Key Hokama,Leonardo N Moraes,Paula O M Hokama,Juliana Capannacci,Célia Regina Nogueira,Sarah S Cury,Robson Francisco Carvalho

doi:10.3390/ijms221910216

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.

Highlights

Chronic myeloid leukemia (CML) was the first leukemia described in the literature, by Rudolf Virchow and John Hughes Bennett in 1845 [1]
Followed by the identification of the chimeric BCR-ABL1 oncogene resulting from the translocation of the BCR gene on chromosome 22 and ABL (Abelson leukemia virus) gene on chromosome 9 that encodes an elevated activity of oncoprotein tyrosine kinase [2]
Three mechanisms are involved in CML oncogenesis, based on BCR-ABL1 activity: (a) altered cell adhesion to the bone marrow stroma and extracellular matrix, (b) constitutively active mitogenic signaling with reduced apoptosis of hematopoietic stem cells and progenitor cells, and (c) genetic instability leading to disease progression [4]

Summary

Introduction

Chronic myeloid leukemia (CML) was the first leukemia described in the literature, by Rudolf Virchow and John Hughes Bennett in 1845 [1]. Over the last 175 years, there have been a number of scientific discoveries involving CML and these have advanced the understanding and treatment of cancer. The understanding of the molecular pathogenesis of CML began with the discovery and correlation of t(9;22)(q34;q11) with the malignancy of the disease [2]. CML is a clonal myeloproliferative neoplasm of hematopoietic stem cells with an incidence in adults of 1–2 cases per 100,000 inhabitants [3]. Three mechanisms are involved in CML oncogenesis, based on BCR-ABL1 activity: (a) altered cell adhesion to the bone marrow stroma and extracellular matrix, (b) constitutively active mitogenic signaling with reduced apoptosis of hematopoietic stem cells and progenitor cells, and (c) genetic instability leading to disease progression [4]

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