Profiling of Chronic Myeloid Neoplasms through RNA Sequencing Analysis

Abstract

Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of hematopoietic stem cells. A higher number of (54%) CML patients in Qatar failed to respond to the treatment compared to those of (34%) internationally. Classification of the different stages of the disease is done in the clinic but is not sufficient; there is a great need to find markers that can be used to stratify the stages of the CML disease and furthermore monitor those that are undergoing treatment. Aims and Objectives: For this study, we aimed to identify the disease-specific profile of genes (transcripts) by analyzing the RNA sequencing of patients, recruited from two different stages of CML disease i.e. Chronic Phase (CP) and Complete Remission (CR). Our objective was to see if we can identify a disease-specific group of transcripts. Methods: A total of 16 subjects were recruited for the study, which included nine patients with chronic phase (CP), three with complete remission and four healthy individuals (Controls, (CNT). RNA extracted from frozen PBMCs or fresh blood was used for RNA sequencing and analysis using Hiseq Illumina 4000. Results and Discussions: We identified a subset of 23 transcripts and classified them into four different groups. We discovered that eight transcripts: MAZ_4, RIT1_3, BUB1_4, CFLAR_5, PARVG_6, SENP5_6, GATS_1, TAOK3_4 were significantly and differentially expressed in the chronic phase patients only compared to five transcripts that segregated the complete remission from the rest of the cohort study and These are HNRNPA3_4, SLC4A7_3, TBC1D4_8, CTC1_1, GRAMD1A_6. The following five transcripts: U2SURP_5SEPT9_2, DPY19L3_8, CYTH4_1, PLXNB2_8 were differentially expressed in both groups of patients compared to control group. These that are shared between CP and CR group might indicate that study subjects in the complete remission did not fully recover and might need closer monitoring and to validate this current observation will be through a longitudinal follow up for some patients in complete remission using other diagnostic methods to examine the ratio of BCR-ABL1 fusion gene and the expression level of these shared transcripts between CP and CR groups. Conclusion: This study provides sets of the promising genes (transcripts) that have the potential to be used to stratify CML patients into complete remission and chronic phase groups. These findings have the potential for following-up and to specifically determine the treatment dose. Furthermore, some of these differentially expressed genes (transcripts) might be a potential therapeutic target or could be used as prognostic biomarkers.