Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

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.

Keywords:

• Chronic lymphocytic leukemia
• lenalidomide
• clinical response
• SHISA3
• Wnt signaling

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1339872.

Additional information

Funding

This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro [AIRC IG14376] to R.Mar and [TRIDEO 16923] to R. Maf, and [AIRC/FIRC #16430] to S.Fio and Ricerca Finalizzata Giovani Ricercatori 2011-2012, Ministero della Salute [GR-2011-02349282] to R.Maf. Additional research support was received by Celgene (San Diego, CA, USA).