Treating Chronic Myeloid Leukemia with hit CRISPR Therapy
Treating Chronic Myeloid Leukemia with hit CRISPR Therapy
Sahar Eskandari,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Introduction: Introduction and aim: With the development of medications that target oncogene-encoded proteins over the past 20 years, the treatment landscape for a number of cancers has undergone a significant transformation. When the proteins that are encoded by oncogenes are suppressed by particular medications, the tumoral process can be halted or reversed. Oncogenes play a crucial role in human cancer. This can be shown in the case of chronic myeloid leukemia, when one oncogene is responsible for all of the clinical characteristics. Thanks to an inhibitor that was rationally created, the majority of individuals with this condition today enjoy a normal life expectancy. The oncogene is unchanged, the medicine just stops the protein, and only a small percentage of patients can choose to stop their treatment. With the development of genome-editing nucleases, particularly the CRISPR/Cas9 system, it is now possible to eradicate oncogenes. A brand-new therapeutic instrument has been created with virtually no limitations for the treatment of cancer. Recent research supports the idea that the CRISPR/Cas9 system might be the only effective treatment for chronic myeloid leukemia. This study examines the biology of chronic myeloid leukemia as well as the development of the CRISPR system and its potential as a targeted treatment for this condition. This study's objective was to treat chronic myeloid leukemia using CRISPR technology.
Methods: Search Method: The current study with titled Treating Chronic Myeloid Leukemia with CRISPR Therapy by searching scholarly databases such as Google Scholar, Science Direct, Springer, and PubMed for investigating CRISPR in leukemia.
Results: Results: Most of the characteristics of chronic myeloid leukemia are controlled by the constitutively active tyrosine-kinase BCR/ABL1 oncogene, which also plays a critical role in the development and maintenance of the disease. Tyrosine-kinase inhibitors are the first-line treatment for this reason, giving the majority of patients a life expectancy comparable to that of a comparable healthy person. Even though this causes side effects in many people, lifetime oral treatment is necessary because the oncogene is still there. Leukemic stem cells also continue to do nothing, and about 25% of patients exhibit resistance. New therapeutic options are still required as a result. In this case, stopping or removing the oncogenic sequence might be a good treatment choice. Because it can cause a specific DNA double strand break, the development of CRISPR (clustered regularly interspaced short palindromic repeats) technology can provide a conclusive cure. Additionally, it offers complete and long-lasting oncogene deletion, whereas tyrosine kinase inhibitors (TKIs) only guarantee inactivation of the BCR-ABL1 oncoprotein during treatment. Prior to the development of CRISPR/Cas9, it was impossible to turn oncogenes off in humans because CRISPR/Cas9 breaks DNA in a sequence-specific way.
Conclusion: Conclusions: The ability of the CRISPR/Cas9 system to repair acquired mutations in a human myeloid leukemia cell line was originally shown in 2015 by Valletta et al. After that, CRISPR-Cas9 was effectively applied to animal models of genetic disorders. Finally, in 2016, the first CRISPR-Cas9 clinical trials in humans got underway. Chia-Hwa Lee et al. demonstrated a decreased proliferation rate as a result of BCR/ABL1 disruption in 2020 by disrupting ABL1 in the human CML K562 cell line utilizing a CRISPR/Cas9 lentiviral vector. As a result, according to the development of the CRISPR technique and the studies carried out, it can be said Creating an animal model with many genetic modifications used to be a time-consuming and expensive operation, but techniques like CRISPR-Cas9 now make it possible to introduce multiple mutations at once.