Comparison of microRNA Expression Profile in Chronic Myeloid Leukemia Patients Newly Diagnosed and Treated by Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Chronic myeloid leukemia (CML) results from a translocation between chromosomes 9 and 22, which generates the Philadelphia chromosome. This forms BCR/ABL1, an active tyrosine kinase protein that promotes cell growth and replication. Despite great progress in CML treatment in the form of tyrosine kinase inhibitors, allogeneic-hematopoietic stem cell transplantation (allo-HSCT) is currently used as an important treatment alternative for patients resistant to these inhibitors. Studies have shown that unregulated expression of microRNAs, which act as oncogenes or tumor suppressors, is associated with human cancers. This contributes to tumor formation and development by stimulating proliferation, angiogenesis, and invasion. Research has demonstrated the potential of microRNAs as biomarkers for cancer diagnosis, prognosis, and therapeutic targets. In the present study, we compared the circulating microRNA expression profiles of 14 newly diagnosed patients with chronic phase-CML and 14 Philadelphia chromosome-negative patients after allo-HSCT. For each patient, we tested 758 microRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis. The global expression profile of microRNAs revealed 16 upregulated and 30 downregulated microRNAs. Target genes were analyzed, and key pathways were extracted and compared. Bioinformatics tools were used to analyze data. Among the downregulated miRNA target genes, some genes related to cell proliferation pathways were identified. These results reveal the comprehensive microRNA profile of CML patients and the main pathways related to the target genes of these miRNAs in cytogenetic remission after allo-HSCT. These results provide new resources for exploring stem cell transplantation-based CML treatment strategies.

Circulating miRNAs can serve as potential diagnostic biomarkers in chronic myelogenous leukemia patients

“…These miRNAs act as onco-miRs or tumor suppressors and are increased in other cancer types ( Table 2 ). Previous studies on the expression pattern of miR-16-1 in newly diagnosed CML-CP treated with IM have shown that down-regulation of miR-16 can play important roles in myeloid leukemogenesis by regulating cell cycle and apoptosis, as well as targeting multiple oncogenes, including, BCL2, MCL1, CCND1, and WNT3A [32] . Inversely, in the present study and our previous experiment for CML, we surprisingly observed up-regulation of miR-16–1 in this particular disease state ( Fig.…”

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

“…The total RNA amount was determined by the ratios A 260 nm/A 280 nm and A 260 nm/A 230 nm (acceptable when both ratios were greater than 1.8). RNA integrity was ensured by obtaining an RNA integrity number (RIN > 8) using the Agilent 2100 Bioanalyzer (Agilent Technologies, Waldbronn, Germany) [ 65 , 66 ].…”

“…The reverse transcription reaction was performed using the Taqman MicroRNA Reverse Transcription Kit in combination with Megaplex RT Primer Human Pool Set A and B (Thermo Fisher Scientific, Waltham, MA, USA). This reaction transcribed 758 miRNAs and three positive endogenous controls (U6 snRNA, RNU44, and RNU48) and one negative control [ 65 , 66 ].…”

“…For miRNA amplification, the Taqman ® Low Density Array Human MicroRNA Arrays v2.0 (A and B) kit (ABIV ® , Life Technologies, Carlsbad, CA, USA) was used according to the manufacturer´s instructions. Analyses were performed on the ViiA7 platform (ABIV ® ) for a total of 758 miRNAs per patient [ 65 , 66 ].…”

Genetic Biomarkers in Chronic Myeloid Leukemia: What Have We Learned So Far?

“…They act in several gene regulation processes that may end up in complex diseases, such as cancer [125]. The first suggestion that miRNAs are correlated to cancer was in 2002 [126,127], and since then miRNAs have been identified as essential switches in cancer pathology [128]. Moreover, deregulated miRNAs have oncogenic and/or tumor suppressive functional roles [129].…”