Relatively heterogeneous mutations and the epigenetic state converge to generate a convergent transcriptional program in the transition from CML CP to BC. This convergent state is driven, in part, by interplay between the PRC and DNA methylation and can potentially be antagonized by combinatorial inhibition. CNA, copy number alteration; SNV, single-nucleotide variant. See Figure 7C in the article by Ko et al that begins on page 2337.