Document Details

Document Type : Thesis 
Document Title :
Gene Expression Profiling on CML Patients with Philadelphia Translocation
الكشف عن نمط التعبير الجيني على مرضى سرطان الدم المزمن في ناقلات كروموسومات الفيلادلفيا
 
Subject : Faculty of Applied Medical Sciences 
Document Language : Arabic 
Abstract : Background: Tyrosine kinase inhibitors (TKIs) and other targeted medicines are crucial in the management of chronic myeloid leukemia (CML) patients' treatment. However, some patients do continue to experience less favorable outcomes and exhibit resistance to therapy. Therefore, the aim of our study is to conduct whole transcriptome sequencing to assess the differential gene expression profile in CML cases according to the patient’s response to TKI-based therapy. Method: Ten blood samples from CML patients at two different phases (diagnosis stage and relapse stage) were collected. All samples were subjected to RNA extraction, and ≤20 µg of RNA was used for NGS sequencing. The DESeq2 R software was used to do the data analysis. Result: A list of 499 genes was found to have significantly differential expression levels among the two study groups. Around 122 genes were found to be upregulated, whereas 377 were found to be downregulated. There was a highly significant deregulation of NTRK2 (>+5 FoldChange) and KRT17 (< -5 FoldChange) expression compared to other genes. The majority of the expressed genes are involved in the cell cycle, PI3K-AKT signaling pathway, cellular senescence, oxidative phosphorylation, microRNA in cancer, FOXO and P53 signaling pathways, as well as other biological processes. Conclusions: Our findings reveal the association between the signaling pathways and treatment resistance in CML cases. These pathways also showed a higher performance in downstream signaling of the TKI target, BCR-ABL. Few target genes require further validation in a larger cohort to confirm their association with TKI resistance. This research finding sheds light on several BCR-ABL independent mechanisms that could be associated with the resistance mechanism, which will improve future treatment of CML patients. Key Words: Chronic Myeloid Leukemia (CML), Philadelphia, Tyrosine Kinase inhibitor, gene expression, Next generation sequencing (NGS). 
Supervisor : Dr. Heba A Alkhatabi 
Thesis Type : Master Thesis 
Publishing Year : 1444 AH
2023 AD 
Added Date : Monday, July 3, 2023 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
صفاء محمد الدهلويAlDahlawi, Safaa MohammedResearcherMaster 

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