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Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide
Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

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.

Chronic lymphocytic leukemia, clinical response, lenalidomide, SHISA3, Wnt signaling
1042-8194
423-433
Maffei, Rossana
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Fiorcari, Stefania
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Martinelli, Silvia
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Benatti, Stefania
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Bulgarelli, Jenny
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Rizzotto, Lara
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Debbia, Giulia
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Santachiara, Rita
01785ae1-62f5-4fc1-bc58-103edb32d39e
Rigolin, Gian Matteo
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Forconi, Francesco
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Rossi, Davide
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Laurenti, Luca
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Palumbo, Giuseppe A.
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Vallisa, Daniele
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Cuneo, Antonio
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Gaidano, Gianluca
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Luppi, Mario
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Marasca, Roberto
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Maffei, Rossana
8b0bb5d0-d00f-4d7f-bbf2-d8dd79b5c795
Fiorcari, Stefania
3ec029c0-ae7d-4606-8414-9ff845b41f40
Martinelli, Silvia
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Benatti, Stefania
b6174c73-39cd-4ef1-8b7d-a7c53b651595
Bulgarelli, Jenny
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Rizzotto, Lara
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Debbia, Giulia
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Santachiara, Rita
01785ae1-62f5-4fc1-bc58-103edb32d39e
Rigolin, Gian Matteo
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Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a
Laurenti, Luca
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Palumbo, Giuseppe A.
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Vallisa, Daniele
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Cuneo, Antonio
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Gaidano, Gianluca
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Luppi, Mario
3ff1e5ea-da23-4674-8c6b-e0ef0269d7bf
Marasca, Roberto
918148d0-8f99-4a29-8322-1b34f6d7dd00

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), pp. 423-433. (doi:10.1080/10428194.2017.1339872).

Record type: Article

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.

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More information

Accepted/In Press date: 26 May 2017
e-pub ahead of print date: 22 June 2017
Published date: 1 February 2018
Keywords: Chronic lymphocytic leukemia, clinical response, lenalidomide, SHISA3, Wnt signaling

Identifiers

Local EPrints ID: 417444
URI: https://eprints.soton.ac.uk/id/eprint/417444
ISSN: 1042-8194
PURE UUID: a53b8556-8de7-46ce-8763-5e280b9d080a

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Date deposited: 31 Jan 2018 17:30
Last modified: 31 Jan 2018 17:30

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Contributors

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

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