A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma

Results from the Fondazione Italiana Linfomi MCL-0208 trial

Riccardo Bomben, Simone Ferrero, Tiziana D'Agaro, Michele Dal Bo, Alessandro Re, Andrea Evangelista, Angelo Michele Carella, Alberto Zamò, Umberto Vitolo, Paola Omedè, Chiara Rusconi, Luca Arcaini, Luigi Rigacci, Stefano Luminari, Andrea Piccin, Delong Liu, Adrian Wiestner, Gianluca Gaidano, Sergio Cortelazzo, Marco Ladetto & 1 others Valter Gattei

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mantle cell lymphoma patients have variable clinical courses, ranging from indolent cases that do not require immediate treatment to aggressive, rapidly progressing diseases. Thus, diagnostic tools capable of stratifying patients according to their risk of relapse and death are needed. This study included 83 samples from the Fondazione Italiana Linfomi MCL-0208 clinical trial. Through gene expression profiling and quantitative real-time PCR we analyzed 46 peripheral blood and 43 formalin-fixed paraffin-embedded lymph node samples. A prediction model to classify patients was developed. By analyzing the transcriptome of 27 peripheral blood samples, two subgroups characterized by a differential expression of genes from the B-cell receptor pathway (B-cell receptorlow and B-cell receptorhigh) were identified. The prediction model based on the quantitative real-time PCR values of six representative genes (AKT3, BCL2, BTK, CD79B, PIK3CD, and SYK), was used to classify the 83 cases (43 B-cell receptorlow and 40 B-cell receptorhigh). The B-cell receptorhigh signature associated with shorter progression-free survival (P=0.0074), selected the mantle cell lymphoma subgroup with the shortest progression-free survival and overall survival (P=0.0014 and P=0.029, respectively) in combination with high (>30%) Ki-67 staining, and was an independent predictor of short progression-free survival along with the Mantle Cell Lymphoma International Prognostic Index-combined score. Moreover, the clinical impact of the 6-gene signature related to the B-cell receptor pathway identified a mantle cell lymphoma subset with shorter progression-free survival intervals also in an external independent mantle cell lymphoma cohort homoge-nously treated with different schedules. In conclusion, this 6-gene signature associates with a poor clinical response in the context of the MCL-0208 clinical trial. (clinicaltrials.gov identifier: 02354313).

Original languageEnglish
Pages (from-to)849-856
Number of pages8
JournalHaematologica
Volume103
Issue number5
DOIs
Publication statusPublished - Apr 30 2018

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Mantle-Cell Lymphoma
B-Lymphocytes
Survival
Disease-Free Survival
Genes
Real-Time Polymerase Chain Reaction
Clinical Trials
Gene Expression Profiling
Transcriptome
Paraffin
Formaldehyde
Appointments and Schedules
Lymph Nodes
Staining and Labeling
Gene Expression
Recurrence

ASJC Scopus subject areas

  • Hematology

Cite this

A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma : Results from the Fondazione Italiana Linfomi MCL-0208 trial. / Bomben, Riccardo; Ferrero, Simone; D'Agaro, Tiziana; Dal Bo, Michele; Re, Alessandro; Evangelista, Andrea; Carella, Angelo Michele; Zamò, Alberto; Vitolo, Umberto; Omedè, Paola; Rusconi, Chiara; Arcaini, Luca; Rigacci, Luigi; Luminari, Stefano; Piccin, Andrea; Liu, Delong; Wiestner, Adrian; Gaidano, Gianluca; Cortelazzo, Sergio; Ladetto, Marco; Gattei, Valter.

In: Haematologica, Vol. 103, No. 5, 30.04.2018, p. 849-856.

Research output: Contribution to journalArticle

Bomben, R, Ferrero, S, D'Agaro, T, Dal Bo, M, Re, A, Evangelista, A, Carella, AM, Zamò, A, Vitolo, U, Omedè, P, Rusconi, C, Arcaini, L, Rigacci, L, Luminari, S, Piccin, A, Liu, D, Wiestner, A, Gaidano, G, Cortelazzo, S, Ladetto, M & Gattei, V 2018, 'A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma: Results from the Fondazione Italiana Linfomi MCL-0208 trial', Haematologica, vol. 103, no. 5, pp. 849-856. https://doi.org/10.3324/haematol.2017.184325
Bomben, Riccardo ; Ferrero, Simone ; D'Agaro, Tiziana ; Dal Bo, Michele ; Re, Alessandro ; Evangelista, Andrea ; Carella, Angelo Michele ; Zamò, Alberto ; Vitolo, Umberto ; Omedè, Paola ; Rusconi, Chiara ; Arcaini, Luca ; Rigacci, Luigi ; Luminari, Stefano ; Piccin, Andrea ; Liu, Delong ; Wiestner, Adrian ; Gaidano, Gianluca ; Cortelazzo, Sergio ; Ladetto, Marco ; Gattei, Valter. / A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma : Results from the Fondazione Italiana Linfomi MCL-0208 trial. In: Haematologica. 2018 ; Vol. 103, No. 5. pp. 849-856.
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AU - D'Agaro, Tiziana

AU - Dal Bo, Michele

AU - Re, Alessandro

AU - Evangelista, Andrea

AU - Carella, Angelo Michele

AU - Zamò, Alberto

AU - Vitolo, Umberto

AU - Omedè, Paola

AU - Rusconi, Chiara

AU - Arcaini, Luca

AU - Rigacci, Luigi

AU - Luminari, Stefano

AU - Piccin, Andrea

AU - Liu, Delong

AU - Wiestner, Adrian

AU - Gaidano, Gianluca

AU - Cortelazzo, Sergio

AU - Ladetto, Marco

AU - Gattei, Valter

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