Expression Profiling of Micro RNAs (MiRNAs) and Long Non-Coding RNAs (lncRNAs) in Chronic Myeloid Leukemia (CML) Patients in the State of Qatar

Abstract

Abstract Background: Myeloproliferative Disorders (MPDs) are defined as clonal hematopoietic disease and are characterized by an overproduction of mature myeloid cells. Chronic Myeloid Leukemia (CML) is the only MPDs that is caused by reciprocal translocation of Abelson murine leukemia gene (ABL) on chromosome 9 and breakpoint cluster region (BCR) on chromosome 22 creating a new chromosome called Philadelphia (Ph) chromosome. Several studies have shown that non-coding RNAs such as microRNAs (MiRNAs) and long non-coding RNAs (LncRNAs) play a crucial role in controlling a variety of cellular process and various types of cancer. In Qatar, CML has a high failure rate of Imatinib treatment up to 54%. This is the first study to profile of validated array of miRNA and lncRNAs at different stages of CML hoping to development better understanding of the disease and help to develop therapeutic intervention for chronic myeloid leukemia patients. Objective: The aim of this study was to provides integrated MiRNAs and LncRNAs expression profiling of CML at different phases to facilitate the development of miRNA and LncRNA targeted therapy. Materials and Methods: A total of 15 peripheral blood samples were collected from CML at three different phases: 5 Chronic phase (CP), 5 Complete Remission (CR), 5 Accelerated Phase (AP) and 5 samples as control. The RNA was extracted from WBCs using QIAamp and reverse transcribed into cDNA using two different protocols. Real-Time Quantitative-Polymerase Chain Reaction (RQ-PCR) array was used to quantify miRNA and LncRNA according to the manufacturer protocols QuantiMir and LncProfilers respectively. Results: Different patterns of MiRNAs and LncRNAs expression in CML phases were identified. Most of MiRNAs were compared to controls, upregulated (x10 or higher) in all phases including: Mi-101-1, Mi-107, Mi-133a, and others. Some MiRNAs were downregulated (0.5 or lower) in some phases including: Let-7 family, Mi-150, Mi-373 and others (Figure 1 and 2). Furthermore, LncRNAs were studied and variety of expression are found at different stages of CML. Generally, most of LncRNAs tend to be more downregulated. This include lncRNAs, Zfas1, H19 and others. Others were upregulated this include: HOTAIR, 18srRNA, IPW, NTT, and others (Figure 3 and 4). Discussion and Conclusions: This study shows the expression profiling of lncRNAs and MiRNAs in CML using RQ-PCR array. In this study, we found high number of aberrantly expressed lncRNAs and MiRNAs in all CML phases. MiRNAs: Most of MiRNAs were oncogenes in all phases which are: Mi-101-1, Mi-107, Mi-10b, Mi-133a, Mi-16, Mi-183, Mi-185, Mi- 195, Mi-19a+b, Mi-126, Mi-23a, and Mi-145 . Other Micro RNAs were tumor supressors in CML phases such as Mi-137 on complete remission Mi-218 on accelerated phase, on chronic phase : Mi- 150, Mi-214, Mi-29a+b+c and others . One study suggests the role of Mi-150 in the pathogenic of CML and particularly in chronic phase. lncRNAs: lncRNAs that serve as tumor suppressors were higher than the oncogenes in complete remission Such as Zfas1. In chronic phase, many lncRNAs were serving as tumor oncogenes such as H19. Recently, a study has revealed that the H19 dysregulation is implicated in CML tumorgenesis and other types of cancers. In accelerated phase, tumor oncogenes are higher than the tumor suppressors. Certainly, it is likely that future work with large number of samples will identify many lncRNA and MiRNAs expressions that serve as biomarkers for the disease. This study shows dysregulation of miRNAs and LncRNAs expression in CML patients. Each stage of the disease shows its pattern of gene expression. Download : Download high-res image (168KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.