PhD Scientific Days 2023

Pathology - Posters C

Germline GATA2 mutations in familial MDS/AML: a manually curated online registry from the ERAPERMED GATA2-HuMo international consortium

Text of the abstract

Background: Pathogenic variants of the GATA2 transcription factor are one of the most common predisposing mutations of familial myeloid malignancies, including acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Although during the past few years a large number of GATA2 mutations have been identified by genetic testing, the number of sizeable cohort studies are still limited, making the clinical interpretation of these variants challenging.

Aims: Our aim was to develop an online, public database of germline GATA2 mutations and associated clinical phenotypes based on international publications to aid the clinical recognition of patients harboring predisposing variants.

Methods: Familial AML/MDS cases with germline variants from 87 case reports and cohort studies published between 2009-2021 were identified via PubMed search and literature review. PubMed search was performed using a combination of keywords ‘GATA2’, ‘deficiency’, ‘mutation’, ‘familial’, ‘acute myeloid leukaemia’, ‘myelodysplastic syndrome’, ‘Emberger-syndrome’ and ‘MonoMac’. Individual cases were uploaded to a self-developed online database, where clinical and pathological findings were classified based on the involvement of different organ systems.

Results: To date, 412 cases with germline GATA2 variants were collected and uploaded to the database. Familial AML and MDS were described in 13.1% (54/412) and 56.8% (234/412) of the patients, respectively. Clinical and histopathologic findings of symptomatic carriers were classified into 15 main categories including hematologic and immunologic features, lymphatic disorders, respiratory tract disorders and other malignancies. Twenty-six further subcategories allow for a more accurate data filtering. In total, 1,484 records are now included in the hierarchically structured dataset with a median 3 (range: 0-16) findings per case. Most recurrent variants of GATA2 were T354M and R396Q, but further analyses are required to assess phenotype-genotype correlations.

Conclusions: Although recent studies have described a large number of germline GATA2 variants, assessment of the mutations’ clinical significance is still an unmet need in the management of patients with familial AML/MDS. Here we developed the first online interactive, public database for the research of phenotype-genotype correlations in this entity.
Funding: ÚNKP-22-3-II-SE-21, SE 250+ Excellence Grant