الفهرس 
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Abstract
To summarize, generation of iPSCs from 7 MDS patients’ samples was successful although only 2 patients had the required SF3B1 mutation for the study. These iPSCs were characterized and showed markers of pluripotency and it was proven that they are vector- free. CD34+ differentiation of the cells was performed and upon culturing these cells in CFA, SF3B1 mutant clones show no significant growth of any haematopoietic progenitor cells. This result was found to complement the published data as a published paper has found that the ability SF3B1 mutant clones to generate myeloid and erythroid colonies was significantly reduced (Mortera-Blanco et al., 2017). Also a poster has provided direct evidence that MDS-associated SF3B1 mutations induces aberrant erythroid maturation and impairs homeostasis of hematopoietic precursor cells with overall disturbance of normal haematopoiesis (Minella et al., 2013) SF3B1 mutant iPSCs showed abnormal cryptic splicing events on ABCB7 gene and this was consistent with the paper previously mentioned (Dolatshad et al., 2016), although the results of aberrant splicing of ips-derived CD34+ cells of SF3B1 mutation was controversial and not conclusive. In addition to that, drug screening was done and Sudemycin D6 showed potential inhibition of SF3B1 which was also proven in a published paper stating that Sudemycin effectively disturb alternative splicing in CLL cells (Xargay-Torrent et al., 2015). On the other hand, benzimidazole anthelmintic despite showing inhibition of SF3B1 mutation in this research, it was not tested before on this specific mutation. R-Loop accumulation and associated DNA damage was observed with this mutation. Application of CRISPR/Cas9 technology for gene editing was done and preliminary results has proven that knock in/out of DNMT3A mutation with various forms of repair was performed. Future direction: In order to complete all the research objectives, knock out of DNMT3A mutation in iPSCs of MDS #1 SF3B1 mutant clone using the CRISPR/Cas9 system will need to be processed. Consequently, comparing both gene edited iPSCs (DNMT3A corrected and introduced) can be illustrated using these techniques1- CD34+ differentiation2- Methocult and adding the cells to CFA3- RNA sequencing4- MeDIP sequencing (which is a genome-wide purification technique that is used to enrich for methylated DNA sequences).