Kotmayer, LiliRomero-Moya, DamiàMarin-Bejar, OskarKozyra, EmiliaCatalà, AlbertBigas Salvans, AnnaWlodarski, Marcin W.Bödör, CsabaGiorgetti, Alessandra2022-10-132022-10-132022Kotmayer L, Romero-Moya D, Marin-Bejar O, Kozyra E, Català A, Bigas A, et al. GATA2 deficiency and MDS/AML: experimental strategies for disease modelling and future therapeutic prospects. Br J Haematol. 2022 Jun 26:1-14. DOI: 10.1111/bjh.183300007-1048http://hdl.handle.net/10230/54365The importance of predisposition to leukaemia in clinical practice is being increasingly recognized. This is emphasized by the establishment of a novel WHO disease category in 2016 called "myeloid neoplasms with germline predisposition". A major syndrome within this group is GATA2 deficiency, a heterogeneous immunodeficiency syndrome with a very high lifetime risk to develop myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). GATA2 deficiency has been identified as the most common hereditary cause of MDS in adolescents with monosomy 7. Allogenic haematopoietic stem cell transplantation is the only curative option; however, chances of survival decrease with progression of immunodeficiency and MDS evolution. Penetrance and expressivity within families carrying GATA2 mutations is often variable, suggesting that co-operating extrinsic events are required to trigger the disease. Predictive tools are lacking, and intrafamilial heterogeneity is poorly understood; hence there is a clear unmet medical need. On behalf of the ERAPerMed GATA2 HuMo consortium, in this review we describe the genetic, clinical, and biological aspects of familial GATA2-related MDS, highlighting the importance of developing robust disease preclinical models to improve early detection and clinical decision-making of GATA2 carriers.application/pdfengThis is an open access article under the terms of the Creative Commons Attribution- NonCommercial- NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/bjh.18330GATA2 deficiencyAcute myeloid leukaemiaBlood cancerMyelodysplastic syndromesinfo:eu-repo/semantics/openAccess