Research Papers:

Therapeutic Targeting of c-Myc in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

Marie Loosveld, Rémy Castellano, Stéphanie Gon, Armelle Goubard, Thomas Crouzet, Laurent Pouyet, Thomas Prebet, Norbert Vey, Bertrand Nadel, Yves Collette and Dominique Payet-Bornet _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2014; 5:3168-3172. https://doi.org/10.18632/oncotarget.1873

Metrics: PDF 3132 views  |   HTML 3166 views  |   ?  


Marie Loosveld1,2,3,4*, Rémy Castellano5*, Stéphanie Gon1,2,3*, Armelle Goubard5, Thomas Crouzet1,2,3, Laurent Pouyet5, Thomas Prebet6, Norbert Vey6, Bertrand Nadel1,2,3*, Yves Collette5*, Dominique Payet-Bornet1,2,3*

1 Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Université UM 2, 13288 Marseille, France


3 CNRS UMR 7280, 13288 Marseille, France

4 Laboratoire Hématologie, APHM, Marseille, France

5 Centre de Recherche en Cancérologie de Marseille (CRCM) Inserm UMR 1068; Institut Paoli-Calmettes; Aix-Marseille Université UM 105; CNRS UMR 7258, Marseille, France

6 Département d’hématologie, Institut Paoli-Calmettes, Marseille, France.

* contributed equally to this work


Dominique PAYET-BORNET , email:

Bertrand NADEL , email:

Keywords: T-ALL, MYC, JQ1, SAHA

Received: March 20, 2014 Accepted: March 26, 2014 Published: March 27, 2014


T-ALL patients treated with intensive chemotherapy achieve high rates of remission. However, frequent long-term toxicities and relapses into chemotherapy-refractory tumors constitute major clinical challenges which could be met by targeted therapies. c-MYC is a central oncogene in T-ALL, prompting the exploration of the efficacy of MYC inhibitors such as JQ1 (BET-bromodomain inhibitor), and SAHA (HDAC inhibitor). Using a standardized ex vivo drug screening assay, we show here that JQ1 and SAHA show competitive efficiency compared to inhibitors of proteasome, PI3K/AKT/mTOR and NOTCH pathways, and synergize in combination with Vincristine. We also compared for the first time the in vivo relevance of such associations in mice xenografted with human primary T-ALLs. Our data indicate that although treatments combining JQ1 or SAHA with chemotherapeutic regimens might represent promising developments in T-ALL, combinations will need to be tailored to specific subgroups of responsive patients, the profiles of which still remain to be precisely defined.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1873