Differential expression analyses of sequential BM samples collected during different disease stages showed that the acquisition of STAG2- or RUNX1-mutant clones not only rewired MDS HSPCs’ differentiation state towards a myeloid-biased transcriptional signature (Supplementary Fig. 4a) but also changed HSCs’ survival dependence from BCL2-mediated anti-apoptotic pathways to TNFα-induced pro-survival NF-κB signaling, thus enabling HSCs to evade the cytotoxic effects of venetoclax (Fig. 1e and Supplementary Fig. 4b–d). Here, NFKB1 is linked to myelodysplastic syndrome.