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Synergistic Induction of Apoptosis in B-Cell Chronic Lymphocytic Leukemia Cells After Treatment With All-Trans Retinoic Acid in Combination With Interleukin-21 and Rituximab Publisher Pubmed



Abbaszadehgoudarzi K1 ; Shokri F2 ; Hosseini M2 ; Jadidiniaragh F1 ; Ghalamfarsa G3 ; Sabooryaraghi A4, 5, 6
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Iran
  2. 2. Departments of Immunology, Iran
  3. 3. Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Iran
  4. 4. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Iran
  5. 5. Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

Source: Journal of Cancer Research and Therapeutics Published:2016


Abstract

Aim: B-cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world and characterized by the progressive expansion of malignant B lymphocytes in peripheral blood. In spite of advances in sciences to recognize the number of effective agents for the treatment of chronic lymphocytic leukemia (CLL), this leukemia is thought as incurable one. Introducing a new therapy that has a direct effect on B-CLL lymphocytes and no cytotoxic effects on the other cells is a great wish. Materials and Methods: Twenty-one patients with B-CLL were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated from patients' blood samples and were further treated with all-Tans retinoic acid (ATRA), interleukin (IL-21), and rituximab at concentrations of 30 ng/ml, 25 ng/ml, and 4 μg/ml, respectively. ATRA, IL21, and rituximab were used alone or in various combinations and their effects on apoptosis were measured using annexin V-fluorescein isothiocyanate apoptosis detection kit. Result: Treatment of the patients' cells with IL21 and rituximab showed a synergistic effect on the induction of apoptosis, in comparison with untreated CLL cells (P < 0.05). The induction of apoptosis by ATRA in combination with IL21 and rituximab were significantly increased compared to untreated CLL cells as a negative control (P < 0.01). Conclusion: Treatment of patients' PBMCs by ATRA in combination with IL21 and rituximab and also IL21 in combination with rituximab showed synergistic induction of apoptosis compared to untreated CLL cells as a negative control (P < 0.01). It seems that ATRA in combination with IL21 and rituximab activate different pathways of apoptosis (extrinsic pathway, intrinsic pathway, and granzyme B pathway).
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