Preliminary data on microRNA expression profiles in a group of South African patients diagnosed with chronic myeloid leukaemia

Abstract

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...

Alteration in miRNAs expression in paediatric acute lymphocyticleukaemia: Insight into patients' therapeutic response

“…The same results were formerly published on Jurkat, 2 T‐cell leukaemia and T‐cell lymphoma cell lines 23 demonstrated a marked up‐regulation of miR‐21 in different ALL cell lines. This elevation in miR‐21 was documented also in other types of leukaemia including chronic lymphocytic leukaemia (CLL) 19 and chronic myeloid leukaemia (CML) 12 . Moreover, several studies have demonstrated a significant up‐regulation of miR‐21 in various kinds of solid tumours including, lung squamous carcinoma, 22 diffuse large B‐cell lymphoma 23 hepatic, 26 colorectal, 27‐29 breast, ovarian, prostate, pancreatic, thyroid cancer, as well as in glioma 30…”

“…During the last decades, the miRNA expression profile reported relating to the formation and progression of various cancers. 18 Several studies 12,19 have been conducted on miRNA expression in leukaemia, although; few of them were concerned with paediatric ALL. 20,21 Thus, this work was undertaken to monitor the possible variation in miRNAs expression in Egyptian children suffering from ALL.…”

“…MicroRNAs are expressed aberrantly in different types of haematological cancers including leukaemia 11 . In specific haematological cell types, miRNAs have a regulatory function in early haematopoietic differentiation, erythropoiesis, granulopoiesis and megakaryopoiesis 12 . Their expression signature is associated with the pathogenesis of different types of leukaemia 8 …”

“…11 In specific haematological cell types, miRNAs have a regulatory function in early haematopoietic differentiation, erythropoiesis, granulopoiesis and megakaryopoiesis. 12 Their expression signature is associated with the pathogenesis of different types of leukaemia. 8 Among those cancer-related miRNAs, miR-21 acts as an oncomiR by targeting many tumour suppressor genes related to proliferation, apoptosis, invasion, angiogenesis and metastasis.…”

Selection of microRNAs in extracellular vesicles for diagnosis of malignant pleural mesothelioma by in�vitro analysis

“…To date, there have been no reports of using EV-derived hsa-miR-193a-5p and hsa-miR-551b-5p for MPM diagnoses. Plasma-derived and serum-derived hsa-miR-193a-5p have been reported as promising indicators for diagnosing amyotrophic lateral sclerosis (ALS) ( 40 ), ovarian cancer ( 41 ), chronic myeloid leukemia ( 42 ), human T-cell leukemia virus type 1 (HTLV-1) infection ( 43 ), colorectal cancer metastasis ( 44 ), and aortic aneurysms ( 45 ). On the other hand, plasma-derived or serum-derived hsa-miR-551b-5p has been reported as a promising indicator of acute pancreatitis ( 46 , 47 ) and gastric cancer ( 48 ).…”