FLI1 and GATA1 govern TLN1 transcription: new insights into FLI1-related platelet disorders

Germline variations in FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims to elucidate the impact of FLI1 variants on human megakaryocytes and platelets. We assessed the impact of one FLI1 variant (Arg337Gln) on megakaryopoiesis using single-cell RNA sequencing, and defects were confirmed in platelet samples obtained from the five patients belonging to four different families carrying the Arg337Gln, Lys345Asp Arg340Cys and Lys345Asp and cell lines.