Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

Maffei, Rossana, Fiorcari, Stefania, Martinelli, Silvia, Benatti, Stefania, Bulgarelli, Jenny, Rizzotto, Lara, Debbia, Giulia, Santachiara, Rita, Rigolin, Gian Matteo, Forconi, Francesco, Rossi, Davide, Laurenti, Luca, Palumbo, Giuseppe A., Vallisa, Daniele, Cuneo, Antonio, Gaidano, Gianluca, Luppi, Mario and Marasca, Roberto (2018) Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide. Leukemia and Lymphoma, 59 (2), 423-433. (doi:10.1080/10428194.2017.1339872).

Abstract

Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients. However, CLL patients sensitive to lenalidomide clearly show a peculiar gene expression profile in leukemic cells. The most up-regulated gene (fold change = +23 in R vs. NR) is Wnt inhibitor SHISA homolog 3 (SHISA3). SHISA3^highCLL are characterized by a restrained activation of Wnt signaling and sensibility to lenalidomide-induced apoptosis. In conclusion, SHISA3 is a candidate gene for the identification of CLL patients who will benefit of lenalidomide treatment as single agent.

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Contributors

Author: Francesco Forconi

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