INTERNATIONAL CONGRESS OF
CancerGenetics
The Role of CRISPR In Cancer Treatment in Chronic Myeloid Leukemia
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Arezoo Hassani,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
- Introduction: 15% of all new instances of leukemia are caused by the myeloproliferative disease chronic myeloid leukemia (CML), which has an incidence of 1-2 cases per 100,000 years. It does not often occur in children and is more common in adults, with a mean age of incidence of roughly 55 years. Both sexes may be affected, however, men are affected at a somewhat higher rate than women—2.2 men for every 100,000 affected compared to 1.4 women. The majority of CML patients experience fatigue, anaemia, splenomegaly, stomach pain, and recurrent infections as their primary clinical symptoms. On the other hand, a lot of asymptomatic people receive a diagnosis following an unrelated medical evaluation. The quantity of scholarly publications detailing CRISPR/Cas9 research in the context of leukemia research has skyrocketed over the past five years. Many of them are related to in vitro research aimed at elucidating the function of various genes in the development of leukemia. These investigations pinpoint important genes that CRISPR/Cas9 technology will later be used to modify in leukemic cells. This study sought to determine how CRISPR functions in the therapy of cancer in CML
- Methods: The present was done by searching scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
- Results: The results have shown the CRIPSR/Cas9 system's potential. A single oncogene drives the malignancy of CML, which is an HSC. CML is a prime target for gene therapy because of the unique characteristics of HSCs, which maintain the long-term production of all hematopoietic lineages. Given the unique properties of self-renewing and multipotent HSCs, it is likely that all daughter cells will acquire any gene editing or CRISPR ablation, hence regaining hematopoiesis. Additionally, the characteristics of the hematopoietic compartment, which permit HSC collection and reinfusion, facilitate the creation of ex vivo treatments and, in turn, the assessment and choice of the modified HSCs, enhancing the procedure's safety and effectiveness. The understanding that the BCR/ABL1 fusion is the fundamental cause of CML pathogenesis is the basis of imatinib therapy. This is why one could reasonably assume that the BCR/ABL1 gene disruption caused by CRISPR/Cas9 would provide a permanent treatment. The capacity to disrupt the BCR/ABL1 oncogene has been the subject of several recent research, demonstrating the potential of the CRISPR-Cas9 system as a therapeutic tool that is about to enter clinical trials. The potential of CRISPR/Cas9 to eliminate the BCR/ABL1 gene fusion has been investigated in several recent in vitro and in vivo investigations. In 2017, Garcia-Tuñón et al. showed for the first time that the BCR/ABL1 oncogene's tumorigenic activity can be reversed by the CRISPR/Cas9 system. In an animal model of CML xenograft, they demonstrated how modified CRISPR cells lost their capacity to divide and survive, and that when the edited cell was chosen, no tumors appeared. Their findings established the fundamental idea that the CRISPR system's abrogation of BCR/ABL1 causes a decrease in tumorigenicity.
- Conclusion: The biggest drawback of in vivo CRISPR therapy, similar to other gene therapy techniques, is the challenge of determining the most effective and secure delivery mechanism. However, new Cas proteins should be used, and humans' innate adaptive immunity to Cas9 proteins could be taken into account. It is also necessary to find a solution for the CRISPR off-target problem. Although the CRISPR-Cas9 system can cause unwanted cleavages outside of on-target sites, it also produces double-strand breaks (DSBs) at target loci in genomic DNA. Gene disruption may occur as a result of mutations brought on by cleavage at off-target locations. A remedy will soon be available thanks to efforts to find new Cas variants with high fidelity and a protospacer neighbouring motif that is less limiting than the NGG sequence. However, in haematological cancers that are clinically treated, like BCR/ABL1 disruption in CML, ensuring the absence of unmodified cells is crucial. In conclusion, a plethora of studies and clinical trials have strongly shown the tremendous therapeutic promise of the CRISPR/Cas tools. This technique has certain technical restrictions, but the number of workarounds for those restrictions has grown at a similar rate. We are certain that CRISPR/Cas gene therapy will become a routine clinical practice soon
- Keywords: CRISPR, cancer, Chronic myeloid leukemia
