Frequent events and molecular pathways involved in immune BMF syndrome. In immune BMF syndrome, T cells, with or without somatic mutations (eg, on STAT3) undergo clonal expansion and activation. This occurs after recognizing unknown antigens, causing the T cells to polarize to type 1 T helper cell response and stimulate cytotoxic T cells. Excessive production of proinflammatory cytokines like IFN-γ and TNF-α and cytotoxic T lymphocytes lead to HSPC destruction via Fas/Fas ligand (FasL) and the TNF-α and receptor apoptosis pathway. Newly identified (by scRNA-seq) ligand–receptor pairs such as TGF-βR3/TGF-β1, TNFSF10/FasL, and CCL5/CCR5 also contribute to cell–cell interactions in this process. B cells exhibit distinct BCR usage and interact with other cell types through ligand–receptor pairs such as NCR3/BAG6, CD47/LGALS9, and ALOX5/ALOX5AP. NK cells play an immunomodulatory role in AA. Somatic mutations and chromosomal abnormalities are prevalent and participate not only in CH but also contribute to an inflammatory phenotype through cell-autonomous and non–cell-autonomous effects. Alternative splicing is observed in AA and MDS, contributing to lineage bias. Figure created with BioRender.com.