Yavuz, TunzaleKaymaz, Burcin TezcanliCelik, BesneTakanlou, Leila SabourAlcitepe, İlaydaTakanlou, Maryam SabourAvci, Cigir Biray2024-08-312024-08-3120241016-91132147-6500https://search.trdizin.gov.tr/tr/yayin/detay/1227908https://hdl.handle.net/11454/103724Aim: Chronic myeloid leukemia (CML) displays a constitutive tyrosine kinase (TK) activity which in turn leads to the activation of various signaling pathways and the outcome of leukemic phenotype. Activated STAT5A and STAT5B from JAK/STAT pathway induce cell growth, proliferation, differentiation, and survival of leukemic cells which are promoted by a cytokine network. Since the second-generation tyrosine kinase inhibitor nilotinib has the advantage of inhibiting this oncogenic TK activity; we aimed to investigate the underlying mechanism of its therapeutic approach and how it induced apoptosis via analyzing the forthcoming molecular targets of the pathway. Materials and Methods: By Nilotinib treatments, cell viability and proliferation assays, apoptotic analysis, expressional regulations of STAT5A&5B mRNA transcripts, protein expression levels, and also cytokines’ expressional assessments were determined in CML model K562 cells, in vitro. Results: Nilotinib treatment in a time and dose-dependent manner assessed a therapeutic approach by decreasing leukemic cell proliferation and survival; inducing leukemic cell apoptosis, down regulating STAT5A&5B mRNA, and protein expression levels, and regulating cytokine expressional network. Conclusion: Nilotinib-mediated therapeutics could be dependent on targeting JAK/STAT pathway members STAT5A and STAT5B, besides; regulating the cytokine network might be another underlying mechanism for sensitization and response of K562 cells to nilotinib in leukemia pathogenesis.eninfo:eu-repo/semantics/openAccessNilotinibchronic myeloid leukemiaJAK/STAT pathwaycytokinesapoptosis.Article6311241351227908