The ERAPERMED project, funded under the grant number 01KU1904, set out to deepen the understanding of GATA2 deficiency, a rare germline disorder that predisposes children and adolescents to myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The consortium comprised four research partners, with the centre led by Dr. Wlodarski (Partner 3) responsible for the first two work packages. The project was carried out during the COVID‑19 pandemic, yet the planned milestones were largely met without significant delays, and the budget was used efficiently and sparingly.

A central technical achievement was the establishment of an interactive genotype‑phenotype database for GATA2 mutations. The team first compiled data from the literature and published a review article summarising germline predisposition in myeloid neoplasms. They then created a provisional database that incorporated 281 germline mutations identified in 554 published cases of AML/MDS between 2009 and 2020, and added 177 unpublished cases from the consortium’s biobank. Each mutation was annotated for type (missense, nonsense, splice‑site, etc.), location within the GATA2 protein, frequency in the general population, and associated haematological and non‑haematological phenotypes. Analysis revealed that missense mutations cluster in the second zinc‑finger domain, whereas truncating mutations are distributed throughout the protein. Regulatory variants in intron 4 were also characterised, showing alterations in E‑box, GATA, or ETS motifs. The database structure, illustrated in the project’s figures, links clinical phenotypes—including cytogenetics—to specific genetic alterations, providing a foundation for future genotype‑phenotype correlation studies that are scheduled for publication at the end of 2023.

Parallel to database development, the consortium analysed the largest cohort of transplanted GATA2‑deficient patients to date. Survival outcomes for patients with GATA2‑associated MDS were comparable to those without germline mutations, and no significant association was found between morbidity and particular mutation types. These findings support the recommendation that early haematopoietic stem‑cell transplantation (HSCT) should be considered for all GATA2‑deficient patients with MDS, irrespective of the underlying mutation. The project also identified clinically relevant biomarkers that will inform personalised treatment algorithms in forthcoming follow‑up studies.

The work package on functional investigations, carried out in vitro and in vivo, aimed to model recurrent GATA2 mutations in inducible pluripotent stem cells and xenograft mouse systems. While detailed results from these experiments are pending, the infrastructure—including a pre‑existing Illumina MiSeq platform, biobanking facilities, and bioinformatics pipelines—was fully operational from the outset, enabling rapid genomic analyses and the discovery of new germline and somatic alterations.

Throughout the project, the consortium maintained a robust governance structure, with regular data‑sharing meetings and a centralised biobank that ensured pseudonymised patient data were securely stored and accessible to all partners. The cost‑neutral extension allowed the team to complete the planned analyses without compromising the timeline. In summary, the ERAPERMED project successfully delivered a comprehensive GATA2 mutation registry, clarified the distribution of pathogenic variants, demonstrated the clinical relevance of early HSCT, and laid the groundwork for future personalised therapeutic strategies.