Together, these data provide a rationale for the selective use of BCL-2 and NF-κB pathway inhibitors to treat the majority of CMP-pattern and GMP-pattern patients with MDS, respectively, whose disease has progressed despite HMA therapy, and they reveal a means to improve patient stratification in ongoing clinical trials of venetoclax-based therapy for these patients. Here, NFKB1 is linked to myelodysplastic syndrome.