Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Jenny Bulgarelli, Lara Rizzotto, Giulia Debbia, Rita Santachiara, Gian Matteo Rigolin, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A. Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca

Research output: Contribution to journalArticle

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). SHISA3highCLL 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.

Original languageEnglish
Pages (from-to)423-433
Number of pages11
JournalLeukemia and Lymphoma
Volume59
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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B-Cell Chronic Lymphocytic Leukemia
Phase II Clinical Trials
Genetic Association Studies
Transcriptome
Natural Killer Cells
Dendritic Cells
Monocytes
Therapeutics
lenalidomide
Apoptosis
Cytokines
T-Lymphocytes
Gene Expression
Pharmaceutical Preparations
Genes

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Maffei, R., Fiorcari, S., Martinelli, S., Benatti, S., Bulgarelli, J., Rizzotto, L., ... Marasca, R. (2018). Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide. Leukemia and Lymphoma, 59(2), 423-433. https://doi.org/10.1080/10428194.2017.1339872

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; Marasca, Roberto.

In: Leukemia and Lymphoma, Vol. 59, No. 2, 01.02.2018, p. 423-433.

Research output: Contribution to journalArticle

Maffei, R, Fiorcari, S, Martinelli, S, Benatti, S, Bulgarelli, J, Rizzotto, L, Debbia, G, Santachiara, R, Rigolin, GM, Forconi, F, Rossi, D, Laurenti, L, Palumbo, GA, Vallisa, D, Cuneo, A, Gaidano, G, Luppi, M & Marasca, R 2018, 'Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide', Leukemia and Lymphoma, vol. 59, no. 2, pp. 423-433. https://doi.org/10.1080/10428194.2017.1339872
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 ; Marasca, Roberto. / Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide. In: Leukemia and Lymphoma. 2018 ; Vol. 59, No. 2. pp. 423-433.
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