Phenotypic and functional characterization of subpopulation of Imatinib resistant chronic myeloid leukemia cell line
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Urban & Partner Sp Z O O
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Purpose: Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the presence of BCR-ABL protein. Imatinib (IMA) is considered as the first line therapy in management of CML which particularly targets the BCR-ABL tyrosine kinase protein. However, emergence of resistance to IMA hinders its clinical efficiency. Hence, identifying novel targets for therapeutic approaches in CML treatment is of great importance. Here, we characterize a new subpopulation of highly adherent IMA-resistant CML cells that express stemness and adhesion markers compared to naive counterparts.Materials and methods: We performed several experimental assays including FISH, flow cytometry, and gene expression assays. Additionally, bioinformatics analysis was performed by normalized web-available microarray data (GSE120932) to revalidate and introduce probable biomarkers. Protein-protein interactions (PPI) network was analyzed by the STRING database employing Cytoscape v3.8.2.Results: Our findings demonstrated that constant exposure to 5 & mu;M IMA led to development of the adherent phenotype (K562R-adh). FISH and BCR-ABL expression analysis indicated that K562R-adh cells were derived from the original cells (K562R). In order to determine the role of various genes involved in epi-thelial-mesenchymal transition (EMT) and stem cell characterization, up/down-regulation of various genes including cancer stem cell (CSC), adhesion and cell surface markers and integrins were observed which was similar to the findings of the GSE120932 dataset.Conclusion: Treating CML patients with tyrosine kinase inhibitors (TKIs) as well as targeting adhesion molecules deemed to be effective approaches in prevention of IMA resistance emergence which in turn may provide promising effects in the clinical management of CML patients.
Açıklama
Anahtar Kelimeler
Chronic Myeloid Leukemia, Drug Resistance, Epithelial -Mesenchymal Transition, Phenotype Switching, Tyrosine Kinase Inhibitors
Kaynak
Advances In Medical Sciences
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
68
Sayı
2
