Signal transducers and activators of transcription (STAT) proteins are latent cytoplasmic transcription factors that affect several cellular processes including cell growth, proliferation, differentiation, and survival. Following phosphorylation, STATs are activated, and their upregulated expressions increase in malignancies with playing a role in the development of leukemia. In this study, transfection of K-562 cells with either unmodified or chemically modified anti-STAT3, -STAT5A, -STAT5B siRNAs for duration of 12 days, determining gene silencing at mRNA and protein levels, evaluating apoptosis rate, and detecting JAK/STAT pathway members' gene expression profiles via array method were aimed. Quantitative RT-PCR and Western blot assays indicated that STAT expressions were downregulated both at mRNA and protein levels, and TUNEL assay showed that leukemic cell apoptosis was induced due to inhibition of STATs. Array analysis resulted with decreases in signal transducer, phosphorylation inducer, and oncogene expressions, whereas increased expressions in STAT inhibitor and apoptosis inducer genes were observed. These results point out that siRNA application could constitute a new and alternative curative method for supporting therapy of CML-diagnosed patients in the future.
STAT proteins are cytoplasmic transcription factors that are involved in the regulation of numerous cellular activities such as cell growth, differentiation, and survival. In this study, we aimed to identify the expression pattern of STAT genes in imatinib-sensitive and -resistant K562 cells, and further, to reveal the effects of STAT5A siRNA knockdown on cell growth and apoptosis induction. The XTT cell proliferation assay showed that both sensitive and resistant K562 cells were sensitized to imatinib upon transfection with STAT5A siRNA. Caspase-3 enzyme activity was increased significantly in both cells. These results may open up new opportunities to overcome chemotherapeutic resistance in leukemia.
ObjectivesRituximab is a monoclonal antibody that targets the B-lymphocyte surface antigen CD20. It is used in the treatment of some diseases including B-cell chronic lymphocytic leukemia (B-CLL). There are a lot of data regarding effect of Rituximab on lymphoma cells. But, there is no satisfactory information about the effect of Rituximab on the signaling pathways in leukemia cells. In this study, it was aimed to understand the effect of Rituximab on JAK-STAT and NF-κB signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) and B-CLL.Material and methodsApoptotic effect of Rituximab in the TANOUE (B-ALL) and EHEB (B-CLL) cell lines were evaluated by using the Annexin V method. mRNA expression levels of STAT3 and RelA were analysed by quantitative RT-PCR (Q-PCR). Alterations in STAT3 and RelA protein expressions were detected by using a chromogenic alkaline phosphatase assay after Western Blotting.ResultsRituximab had no apoptotic effect on both cell lines. Complement-mediated cytotoxicity was only detected in EHEB cells. mRNA and protein expressions of STAT3 and RelA genes were decreased following Rituximab treatment.ConclusionOur preliminary results suggest that the use of Rituximab might be effective in B-ALL though both signaling pathways.
The aim of this work was to report two cases of hypereosinophilic syndrome (HES). FIP1L1-PDGFRA fusion was assessed with two protocols at RNA level. The fusion transcript was found positive at the RNA level with both PCR methods in two cases. In this study, the efficiency of imatinib treatment and a dramatic response in two HES cases with multisystemic involvement showing the characteristics of a chronic myeloproliferative disease were presented. Both cases showed complete responses confirming that imatinib mesylate treatment could be successful even in patients with advanced HES having myeloproliferative disease.
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