Acquired genetic abnormalities predict outcome in patients with GATA2 deficiency

This work describes 78 patients with GATA2 deficiency followed in France and Belgium. GATA2 is a very important protein for generating blood cells. Defects in GATA2 predispose to immune deficiency and the development of blood cancers at a young age. We first observed correlations between the type of GATA2 alterations and clinical aspects. Indeed, truncated proteins are associated with chronic infections and size-modified proteins with leukaemic development. Patients were then classified according to the morphological appearance of their bone marrow. The search for acquired genetic abnormalities revealed numerous mutations in the STAG2 gene correlating with low leukaemia progression. Conversely, mutations in certain genes (SETBP1, RAS pathway and RUNX1) are identified during leukaemic progression. This study paves the way for better monitoring of progression through biology.

This work allows us to understand the importance of monitoring acquired abnormalities in patients by taking into account clonal dynamics, but also to understand the mechanisms of transformation into leukaemia induced by acquired abnormalities.

Collaborations and acknowledgements

Sponsorship

• Association 111 des arts,
• Toulouse Recherche Enfant Cancer,
• INCA,
• CONNECT-AML,
• Association Constancelapetiteguerriereastronaute

Collaborations

• France : Dr J Donadieu, registre des neutropénies,
• UK : Prof Matthew Collin, Human Dendritic Cell Laboratory, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK