Evaluation and bioinformatic analysis of the genetic origin of acute lymphoblastic leukemia cancer patients and their response to novel chemotherapy drugs
Evaluation and bioinformatic analysis of the genetic origin of acute lymphoblastic leukemia cancer patients and their response to novel chemotherapy drugs
Introduction: Acute lymphoblastic leukemia (ALL) is a relatively rare heterogeneous blood malignancy in adults, but it is one of the most common types of cancer in children, which is characterized by the uncontrolled proliferation of lymphoid progenitor cells in the bone marrow and peripheral blood. ALL is characterized by the rapid development of white blood cell precursors called lymphoblasts, which divide inappropriately and disrupt the production of healthy blood cells, resulting in the production of very low amounts of red blood cells, white blood cells and platelets, which cause anemia, neutropenia and thrombocytopenia respectively. The two main subtypes of ALL, which are classified according to immunophenotype, are B cell ALL (in 85 to 90% of cases) and T cell ALL (in 10 to 15% of cases) are ALL.
This disease is very common in children but also occurs in adults, but the probability of treatment in adults is very low, but in children, treatments are a good opportunity for their recovery. Chemotherapy and radiation exposure may increase the risk of developing ALL. Leukemia treatment means that the cancer is gone, does not recur and no further treatment is needed.
Methods: To conduct this research, prominent sources in the field of bioinformatics and molecular biology were used, including the NCBI database and using Mega-gene pharmacogenetic software. With the help of
this program, we categorized and analyzed the data related to the data management of each gene, the data related to the polymorphism of a gene, and the drug information related to the disease, In order to be able to analyze the polymorphism information of the genes involved in this disease and to diagnose the side effects of medicinal uses with genetic origin of people.
Results: With the investigations entered in Mega-gene, we have reached the processing of common polymorphisms in the occurrence of this disease, which includes, among the 47 genes that are involved in the occurrence of the disease, three genes have the highest percentage. the Effect of a gene is based on its occurrence rate in the statistical population and also the highest number of reports of that gene. Polymorphism refers to the presence of two or more different forms of a particular DNA sequence that can occur in different individuals or populations. The most common type of polymorphism involves changes in SNPs, so each SNP represents a difference in a DNA building block called a nucleotide. As mentioned, among all the genes that are effective in the occurrence of this disease, despite the presence of polymorphism in each of them, these three genes have the highest polymorphism statistics, which include:
1- JAK2 with 48 SNPs and 6.04% influence in the community.
2- RUNX1 with 25 SNPs and 3.14% influence in society.
3- RB1 with 23 SNPs and 2.89% influence in society.
Also, by examining the effects of drug treatment in affected people, despite the existence of polymorphisms in the genes involved in this disease, by examining 24 different drugs in the treatment of ALL, affected patients should not use a number of drugs to treat their symptoms. These six items include:
1- People with MLH1 genetic background, taking the drugs Adriamycin, Thioguanine, Erwinase, Dasatinib and Azacitidine causes side effect of nausea in patients.
2- People with JAK2 genetic background by using Methotrexate, L-Asparaginase and Azacitidine drugs cause side effect of Crohn, Inflammation, Platelet Hyperaggregability and Psoriasis in patients.
3- People with RB1 genetic background by using Etoposide drugs causes side effect of Mucositis in patients.
4- People with TP53 genetic background by using Nelarabine drugs causes side effect of Anorexia in patients.
5- People with BCR genetic background by using Dasatinib drugs causes side effect of Tinnitus in patients.
6- People with IKZF1 genetic background by using Thioguanine drugs causes side effect of Decreased cell growth in patients.
Conclusion: To use drugs to treat the ALL disease Before prescribing medicine and therapy, it is necessary to carry out genetic tests to check the presence of polymorphisms in common genes, including MLH1, JAK2 and RB1 then It should be done on patients so that in case of polymorphism, drugs with less side effects can be prescribed for the patient.