Anaplastic large cell lymphoma is one of the most common pediatric T-lymphomas. It mainly affects CD4 lymphocytes (major guardian of the immune system) and is associated in more than 80% of cases with the NPM-ALK chromosomal translocation (which is the transfer of one chromosome segment to another chromosome).
Anaplastic large cell lymphoma is highly chemosensitive but over 40% of the patients experience several relapses. To better treat these patients it is therefore essential to know the genesis of this cancer.
By forcing normal CD4 lymphocytes to express oncogenic protein from NPM-ALK chromosome translocation, Dr. Fabienne MEGGETTO’s lab, have able to develop a cellular model of anaplastic large cell lymphoma. In collaboration with the bioinformatics division of the Toulouse Cancer Research Centre, a team from the Necker Institute in Paris, and the French establishment of blood in Bordeaux, the analysis of the genome and epigenome (influence of the cell environment on its genome) revealed that tumoral cells expressing oncogene ALK take on the appearance of cancer stem cells of thymic origin. In addition, the team highlighted biological mechanism that regulate them, which could have a significant impact on the clinical prognosis. The prospect of therapies specifically targeting these tumour cells therefore offers new hopes for cancer treatment.
Discover the published article :
J Clin Invest. 2020 Nov 3;134990.doi: 10.1172/JCI134990. Online ahead of print.
ALK-transformed mature T lymphocytes restore early thymus progenitor features
Annabelle Congras, Coralie Hoareau-Aveilla, Nina Caillet, Marie Tosolini, Patrick Villarese, Agata Cieslak, Laura Rodriguez, Vahid Asnafi, Elisabeth Macintyre, Gerda Egger, Pierre Brousset, Laurence Lamant, Fabienne Meggetto
Key words :
- Lymphomas,
- chromosomal translocation,
- (epi)genome,
- stem cells,
- therapy
Contact :
Fabienne MEGGETTO, DR1 CNRS, CN24 – fabienne.meggetto@inserm.fr
Co-team leader of team RNA biology in hematological cancers
Equipe labelisée Ligue 2017
Laboratoire d’Excellence Toulouse Cancer-TOUCAN, F-31024 Toulouse, France
Institut Carnot Lymphome-CALYM, F-31024 Toulouse, France
Collaborations :
- Team of Drs Vahid ASNAFI and Elisabeth MACINTYRE, haematology department/INSERM1151, Institut Necker-Enfants Malades, Paris
- Etablissement Français du Sang – Nouvelle Aquitaine, INSERM U1035, University of Bordeaux, Bordeaux, France.
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