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

doi:10.1080/10428194.2017.1339872

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

Department of Translational Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	423-433
Number of pages	11
Journal	Leukemia and Lymphoma
Volume	59
Issue number	2
DOIs	https://doi.org/10.1080/10428194.2017.1339872
Publication status	Published - 1 Feb 2018

Keywords

Chronic lymphocytic leukemia
SHISA3
Wnt signaling
clinical response
lenalidomide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/10428194.2017.1339872

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Maffei, R., Fiorcari, S., Martinelli, S., Benatti, S., Bulgarelli, J., Rizzotto, L., Debbia, G., Santachiara, R., Rigolin, G. M., Forconi, F., Rossi, D., Laurenti, L., Palumbo, G. A., 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, 59(2), 423-433. https://doi.org/10.1080/10428194.2017.1339872

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title = "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). 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.",

keywords = "Chronic lymphocytic leukemia, SHISA3, Wnt signaling, clinical response, lenalidomide",

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

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year = "2018",

month = feb,

day = "1",

doi = "10.1080/10428194.2017.1339872",

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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

TY - JOUR

T1 - Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

AU - Maffei, Rossana

AU - Fiorcari, Stefania

AU - Martinelli, Silvia

AU - Benatti, Stefania

AU - Bulgarelli, Jenny

AU - Rizzotto, Lara

AU - Debbia, Giulia

AU - Santachiara, Rita

AU - Rigolin, Gian Matteo

AU - Forconi, Francesco

AU - Rossi, Davide

AU - Laurenti, Luca

AU - Palumbo, Giuseppe A.

AU - Vallisa, Daniele

AU - Cuneo, Antonio

AU - Gaidano, Gianluca

AU - Luppi, Mario

AU - Marasca, Roberto

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Chronic lymphocytic leukemia

KW - SHISA3

KW - Wnt signaling

KW - clinical response

KW - lenalidomide

UR - https://www.scopus.com/pages/publications/85021138150

U2 - 10.1080/10428194.2017.1339872

DO - 10.1080/10428194.2017.1339872

M3 - Article

SN - 1042-8194

VL - 59

SP - 423

EP - 433

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

IS - 2

ER -

Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide

Abstract

Keywords

UN SDGs

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