Profiling B cell chronic lymphocytic leukemia by reverse phase protein array: Focus on apoptotic proteins. Issue 5 (16th June 2016)

• Record Type: Journal Article
• Authors: Frezzato, Federica; Accordi, Benedetta; Trimarco, Valentina; Gattazzo, Cristina; Martini, Veronica; Milani, Gloria; Bresolin, Silvia; Severin, Filippo; Visentin, Andrea; Basso, Giuseppe; Semenzato, Gianpietro; Trentin, Livio
• Is Part Of: Journal of leukocyte biology. Volume 100:Issue 5(2016)
• Page Start: 1061
• Page End: 1070
• Publication Date: 2016-06-16
• Subjects: signal transduction -- lymphocyte -- HSP70 -- Smac/DIABLO; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.2AB0715-301R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Identification of molecules involved in apoptosis control (HSP70, Smac/DIABLO, PARP and Caspase-6), to consider in the design of innovative therapies for CLL. Abstract: B cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B lymphocytes from proliferative activity and apoptosis resistance. The increased awareness of the importance of B cell receptor signaling in CLL has raised new opportunities for targeted intervention. Herein, we describe a study performed with the high-throughput RPPA (reverse phase protein array) technique, which allowed us to simultaneously study different molecules in a large series of patients. We analyzed B lymphocytes from 57 patients with CLL and 11 healthy subjects. Different pathways were assessed for activation/expression of key signaling proteins. Data obtained were validated by Western blotting and confocal microscopy. The RPPA investigation and its validation, identified 3 series of proteins: 1) molecules whose expression levels reached statistically significant differences in CLL vs. healthy controls (HSP70, Smac/DIABLO, cleaved PARP, and cleaved caspase-6); 2) proteins with a positive trend of difference in CLL vs. healthy controls (HS1, γ-tubulin, PKC α/β-II Thr-638/641, p38 MAPK Thr-180/Tyr-182, NF-κB Ser-536, Bcl2 Ser-70 and Src Tyr-527); and 3) molecules differentially expressed in patients with IGHV mutations vs. those without mutations (ZAP70, PKC-ζλ, Thr-410/403, and CD45). This study identified some molecules, particularly those involved in apoptosis control, which could be considered for further studies to design new therapeutic strategies in CLL.