To study the underlying molecular mechanisms causing the defect in megakaryocyte development by FLI1 p.Met100*

In this study, we investigated the role of the transcription factor FLI1 in megakaryopoiesis and examined how the newly identified pathological variant, FLI1 p.Met100*, disrupts megakaryocyte and platelet development. We hypothesized that FLI1 p.Met100* would generate a truncated peptide with a dominant negative effect. To test this, we ectopically expressed both wild-type FLI1 and FLI1 p.Met100* in Meg01 cells. Following succeful detection of the truncated peptide, RNA sequencing revealed that FLI1 p.Met100* upregulated erythroid genes, including KLF1, CD235a, and CD36, whereas wild-type FLI1 suppressed their expression. Overall design: To explore this, we lentivirally transduced Meg01 cells with an empty vector (EV), wild-type FLI1, or FLI1 p.Met100* and collected them 3 days after transduction for RNA sequecing analysis. We had four replicates for each condition.