Effects of protein kinase inhibitors on chronic lymphocytic leukemia (CLL) cells

作者: Hasan Imam

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摘要: B cell Chronic lymphocytic leukemia (B-CLL) is a neoplastic disorder characterized by accumulation of lymphocytes due to uncontrolled growth and resistance apoptosis. Src family kinases (SFKs) are non receptor tyrosine present in the cytosol, which couple with downstream signaling thus mediate growth, survival, proliferation antiapoptosis. In CLL cells SFKs remarkably overexpressed, especially Lyn kinase. This gives rational use inhibitor treat CLL. Addition specific pharmacological inhibitors SFKs, bosutinib saracatinib, inhibited global phosphorylation as well basal auto-phosphorylation SFKs. Mechanistically, inhibition coupled apoptosis induction via decreased protein levels anti-apoptotic proteins Bcl-2, Mcl-1 survivin, were demonstrated Western blotting. To assess induction, annexin V binding freshly isolated or without treatment kinase was measured flow cytometrically. Using at concentration 10 μM average percentages V-positive, apoptotic 11 samples increased from 24 % untreated controls 55 %, 45 37 after bosutinib, saracatinib dasatinib, respectively. The response each showed high but comparable degree variation among investigated samples. On induced significantly higher efficiency than calls for further investigation its pre-clinical potential

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