Abstract. Micro-ribonucleic acids (miRNAs) are small functional non-coding RNAs that downregulate gene expression at the post-transcriptional level. Abnormal expression of specific miRNAs has been recorded in chronic lymphocytic leukaemia, other non-Hodgkin B-cell lymphomas, lung cancer and chronic myeloid leukaemia (CML). The aim of this study was to compare miRNA expression profiles among patients with newly diagnosed CML, those on established therapy with imatinib mesylate, and healthy individuals. The expression of 88 miRNAs was evaluated in a total of nine samples divided into three groups: Group 1 comprised three samples collected from newly diagnosed CML patients; group 2 consisted of three samples collected from patients on therapy; the remaining three samples were collected from healthy volunteers (control group). Total RNA was extracted from whole blood and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was performed on the LightCycler ® 480 platform using Human Serum & Plasma miRNA PCR Arrays. In group 1, only SNORD44 was downregulated, while hsa-miR-372 and hsa-miR-375 were found to be significantly upregulated compared with the control group. By contrast, 49 miRNAs were significantly upregulated in group 2 compared with the control group. miRNAs hsa-miR-106b, hsa-miR-21, hsa-miR-221, hsa-miR-10a, hsa-miR-193a-5p and hsa-miR-30e were expressed in group 2. Therefore, miRNA expression profiles differed between the two patient groups.
IntroductionChronic myeloid leukaemia (CML) is an acquired disease resulting from the malignant transformation of a single stem cell, characterized by anaemia extreme blood granulocytosis and granulocytic immaturity (1). CML is triggered by a reciprocal translocation of the long arms of chromosomes 9 and 22, referred to as the Philadelphia chromosome (2). The breakpoint cluster region (BCR) gene on chromosome 22 and the Abelson murine leukaemia viral oncogene homolog 1 (ABL1) gene on chromosome 9 are involved in this t(9;22)(q34;q11) translocation leading to the formation of a new chimeric fusion oncogene, BCR-ABL1. Expression of this fusion oncogene produces an abnormal, elongated 8-kb ribonucleic acid (RNA) fragment, which is translated into a unique tyrosine phosphoprotein kinase, considered to be essential for the development of the leukaemic phenotype (1,3).Imatinib mesylate (Gleevec ® ; Novartis, Basel, Switzerland) has been established as the standard first-line therapy for CML (4,5). Response to therapy is defined as optimal, suboptimal, or failure of treatment. Optimal response is defined as follows: Complete haematological response [normal full blood count, minimal cytogenetic response (CyR) at 3 months]; partial cytogenetic response at 6 months; complete CyR (CCyR) at 12 months and major molecular response (≥3-log reduction in BCR-ABL1 transcripts) at 18 months (6).MicroRNAs (miRNAs) have recently been identified as a class of small functional non-coding RNAs of 18-25 nucleotides (7,8) which bind to the 3'-untranslated region of mRNAs, do...
