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

Dipartimento di Medicina Traslazionale

Risultato della ricerca: Contributo su rivista › Articolo in rivista › 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.

Lingua originale	Inglese
pagine (da-a)	423-433
Numero di pagine	11
Rivista	Leukemia and Lymphoma
Volume	59
Numero di pubblicazione	2
DOI	https://doi.org/10.1080/10428194.2017.1339872
Stato di pubblicazione	Pubblicato - 1 feb 2018

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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",

note = "Publisher Copyright: {\textcopyright} 2017 Informa UK Limited, trading as Taylor & Francis Group.",

year = "2018",

month = feb,

day = "1",

doi = "10.1080/10428194.2017.1339872",

language = "English",

volume = "59",

pages = "423--433",

journal = "Leukemia and Lymphoma",

issn = "1042-8194",

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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, n. 2, pagg. 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

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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

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