The work presented in this article is based on a clinical observation: 3 children from the same family all suffered from B-acute lymphoblastic leukemia (B-ALL). Knowing that it is a very rare disease, we suspected a genetic predisposition and by reading the genome of these three patients we identified a mutation in PAX5, a gene involved in the production of blood cells (process called hematopoiesis). Blood cells are dynamically produced from hematopoietic stem cells in precise proportions and adapted to environmental conditions. Deregulation of hematopoiesis can lead to leukemia such as B-ALL which are both a blockage of the production of functional lymphoid cells (which produce antibodies) and an uncontrolled proliferation of these immature cells (blasts). It is a multi-step process: a first mutation will create a pre-leukemia condition usually without clinical symptoms and other mutations will progress towards leukemia. Here we have shown that the first mutation is inherited what remains an extremely rare event in blood cancers.

This work demonstrates the importance of considering the family origin of leukemia before choosing a compatible donor for a transplant

Discover the published article :

Blood. 2020 Oct 9
Germline PAX5 mutation predisposes to familial B acute lymphoblastic leukemia
Nicolas Duployez, Laura Audrey Jamrog, Vincent Fregona, Camille Hamelle, Laurène Fenwarth, Sophie Lejeune, Nathalie Helevaut, Sandrine Geffroy, Aurelie Caillault Venet, Alice Marceau-Renaut, Stéphanie Poulain, Catherine Roche-Lestienne, Laetitia Largeaud, Nais Prade, Stephanie Dufrechou, Sylvie Hébrard, Céline Berthon, Brigitte Nelken, Jose Fernandes, Céline Villenet, Martin Figeac, Bastien Gerby, Eric Delabesse, Claude Preudhomme, Cyril Broccardo

Key words :

  • Leukemia
  • Predisposition

Contact :

Cyril Broccardo
Equipe : 16 du CRCT (Altération des facteurs de transcription dans les leucémies aigües – Pr. Eric Delabesse)
Mail : cyril.broccardo@inserm.fr

Collaborations :

The team was supported by INSERM, CNRS, Paul Sabatier University, the association « Capucine » and Société Française des Cancers de l’Enfant (SFCE), by Région Occitanie, by the Ligue Nationale Contre le Cancer, the association « les 111 des arts », the association « Cassandra » and the association « Constance La Petite Guerrière Astronaute ». We are grateful to Manon Farcé from the cytometry and cell-sorting facility of the Technology Cluster of the CRCT (INSERM U1037) for technical assistance and the Anexplo/Genotoul platforms for technical assistance (UMS006).

One picture :

Leukemia is a multi-step process: a first mutation will create a pre-leukemia condition generally without clinical symptoms (here mutation in PAX5) and other mutations (additional alterations) will progress towards leukemia.