Oncotarget

Clinical Research Papers:

BACH2 promotes indolent clinical presentation in Waldenström macroglobulinemia

Charles Herbaux, Elisabeth Bertrand, Guillemette Marot, Christophe Roumier, Nicolas Poret, Valérie Soenen, Olivier Nibourel, Catherine Roche-Lestienne, Natacha Broucqsault, Sylvie Galiègue-Zouitina, Eileen M Boyle, Guillemette Fouquet, Aline Renneville, Sabine Tricot, Franck Morschhauser, Claude Preudhomme, Bruno Quesnel, Stephanie Poulain and Xavier Leleu _

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Oncotarget. 2017; 8:57451-57459. https://doi.org/10.18632/oncotarget.9917

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Abstract

Charles Herbaux1,2, Elisabeth Bertrand1, Guillemette Marot3, Christophe Roumier4, Nicolas Poret1, Valérie Soenen4, Olivier Nibourel4, Catherine Roche-Lestienne4, Natacha Broucqsault1, Sylvie Galiègue-Zouitina1, Eileen M Boyle2, Guillemette Fouquet2, Aline Renneville4, Sabine Tricot5, Franck Morschhauser2, Claude Preudhomme4, Bruno Quesnel1,2, Stephanie Poulain5 and Xavier Leleu6,7

1Inserm U837, Team 3, Cancer Research Institute of Lille, Lille, France

2Service des Maladies du Sang, Hôpital Huriez, CHRU, Lille, France

3Lille Nord de France University, Equipe Biostatistique, UDSL, Lille, France

4Laboratory d’Hématologie, Biologie and Pathologie Center, CHRU, Lille, France

5Département d’Hématologie-Immunologie-Cytogénétique, CH, Valenciennes, France

6Service d’Hématolgie et Thérapie cellulaire, Hématologie, CHU, Poitiers, France

7Centre d’Investigation Clinique Inserm, CHU, Poitiers, France

Correspondence to:

Xavier Leleu, email: [email protected]

Keywords: BACH2, Waldenström macroglobulinemia, indolent, progression, physiopathology

Received: February 21, 2016     Accepted: May 12, 2016     Published: June 07, 2016

ABSTRACT

Approximately 30% of the patients who fulfil the criteria of Waldenström’s macroglobulinemia (WM) are diagnosed while asymptomatic (indolent), and will not require immediate therapy. Conversely, patients with a disease-related event will be considered for therapy. The physiopathology of these 2 groups remains unclear, and the mechanisms of progression from indolent to symptomatic WM have yet to be fully understood. Seventeen patients diagnosed with WM were included in this study, 8 asymptomatic WM (A-WM) and 9 symptomatic WM (S-WM). A differential analysis was performed on a first series of 11 patients and identified 48 genes whose expression separated samples from A- to S-WM. This gene signature was then confirmed on a second independent validation set of 6 WM. Within this expression profile, BACH2, a B-cell transcription factor known to be a tumor suppressor gene, was found to be over-expressed in A-MW relatively to S-MW. We specifically over-expressed BACH2 in a WM-related cell line and observed a significant reduction of the clonogenic activity. To the best of our knowledge, we report for the first time a specific gene expression signature that differentiates A-WM and S-WM. Within this expression profile, BACH2 was identified as a candidate gene that may help to understand better the behavior of tumor cells in indolent WM.


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