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Original Article

Determination of drug sensitivity subgroups in acute myeloid leukemia to increase treatment efficacy by imatinib and its analog imatinib B

Can Turk, Esma Eryilmaz Dogan

   

Abstract
While chemotherapeutics without any selective properties were used in cancer treatment in the past, they are now replaced by targeted drugs. Imatinib has common use in the treatment of acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML) but not Acute myeloid leukemia (AML). It is a highly effective oral drug treatment and provides stable remission in many people treated. Treatment of imatinib mesylate can cause various side effects such as swelling around the eyes, nausea, and vomiting. However, it is likely to act on normal cells, and this effect causes side effects. To create a better design with increased bioactivity with decreased possible side effects of imatinib we calculated the molecular pharmaceutical properties and biological activity and investigated its analogs. Also, we figured out which genetically subclasses of AML can benefit from therapy with imatinib analog, imatinib B. The gene expression data were retrieved from the E-MTAB-783 Cancer Genome Project database. Gene expression data for available genes in cell lines belonging to various types of leukemia were chosen for use in the analysis. Three subgroups were determined using all genome expression profiles and drug sensitivity data of AML cell lines associated with imatinib sensitivity. Genes with statistical significance between groups, network connections, and related pathways to which they belong were introduced. Thirty-two genes and 18 pathways that can predict sensitivity to imatinib in AML cell lines were identified. Also, our results show these genes are closely linked with each other. Today, the use of Imatinib in the treatment of AML is limited. By redesigning the imatinib molecule, it will be possible to effectively treat certain AML subgroups by reducing harmful side effects.

Key words: Bioactivity, drug-likeness, drug design, boron, biomarker, imatinib

Med-Science. 2021; 10(3): 828-34

 
 
Medicine Science Vol:10 Issue:3 Year:2021 PP:670–1086
Posted in Vol: 10 Issue: 3 Year: 2021 September pp: 670–1086

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