Figure 7.

Replication changes in leukemia respect normal developmental boundaries. (A) Diagram of normal boundaries of replication in development, defining regions of constitutively early or late replication timing, conserved boundaries between these regions, and developmentally regulated domains. (B). Examples of each class of domains in leukemic fingerprints that switch replication timing (red) against a background of other human cell types (gray) and normal B-cell controls (black). Here, two pan-leukemic fingerprint regions align to both developmental boundaries and timing values. T-cell profiles switch timing in opposite directions from others, but at the same transition region as is used in B cells and other cell types, while an REH-specific fingerprint region aligns to one boundary but switches earlier than other cell types profiled. Additional examples of domain boundary alignment are shown in Supplemental Figure S10. (C) A summary of the number of domains in leukemic fingerprints that align to developmental boundaries, either with or without acquiring the timing of other cell types.