Profiling B cell chronic lymphocytic leukemia by reverse phase protein array: Focus on apoptotic proteins

Identification of molecules involved in apoptosis control (HSP70, Smac/DIABLO, PARP and Caspase‐6), to consider in the design of innovative therapies for CLL. B cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B lymphocytes from proliferative activity and apoptosis res...

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Veröffentlicht in:Journal of leukocyte biology 2016-11, Vol.100 (5), p.1061-1070
Hauptverfasser: Frezzato, Federica, Accordi, Benedetta, Trimarco, Valentina, Gattazzo, Cristina, Martini, Veronica, Milani, Gloria, Bresolin, Silvia, Severin, Filippo, Visentin, Andrea, Basso, Giuseppe, Semenzato, Gianpietro, Trentin, Livio
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Sprache:eng
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Zusammenfassung:Identification of molecules involved in apoptosis control (HSP70, Smac/DIABLO, PARP and Caspase‐6), to consider in the design of innovative therapies for CLL. 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.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.2AB0715-301R