Fig. 3: Mutation accumulation in BCR::ABL1 cells.
From: Timing and trajectory of BCR::ABL1-driven chronic myeloid leukaemia
a, Number of somatic SNVs carried by colonies (n = 834), coloured by driver status (BCR::ABL1, red; other driver mutation, orange; wild-type (WT), blue) and relationship with age, with mixed effects model regression lines and 95% confidence intervals stratified by BCR::ABL1 status (red, BCR::ABL1-positive; grey, BCR::ABL1-negative, model excludes PD57332 due to lack of wild-type, n = 799). b, A phylogenetic tree for an example patient PD51632 with the estimated proportion of SBS signature SBS1, SBSblood and SBS18 contributing to SNVs for each of the branches, categorized into five groups: (1) branches of the BCR::ABL1-positive clonal expansion (‘CML’), (2) ancestral branch of BCR::ABL1 colonies representing the lineage of CML origin (‘pre-CML lineage’), (3) early mutations within the CML (that is, shared branches within the clonal expansion, ‘early CML’, lower shaded purple box), (4) branches of BCR::ABL1-negative colonies (wild-type, WT) and (5) early-in-life mutations representing the top 100 mutations of the phylogenetic tree, upper shaded blue box. c, Bar plot of SBS1, SBSblood and SBS18 proportions contributing to SNV spectra for PD51632, with the height of the bar showing the posterior mean and the error bars representing 95% credibility intervals. d, Bar plot represents the proportion of C>T at CpG changes for PD51632. The height of the bar depicts the observed proportions and the error bars mark the 95% binomial proportion confidence intervals. e, Cohort-wide plots of proportions of C>T at CpGs, SBS1, SBS18 and SBSblood, excluding PD57333 and PD57332 because of absence of either WT or mutant colonies in these patients. The dots represent the mixed effect meta-analysis estimated proportion and the bars 95% confidence intervals. The P values are for a two-sided test of the null hypothesis that the difference between proportions is zero. The P values are not adjusted for multiple testing. f, Per sample dot plot for PD51635, showing C>T at CpG proportion (excluding BCR::ABL1 clade trunk in BCR::ABL1-positive colonies) by sample BCR::ABL1 status, faceted by time of sampling and annotated by per sample driver status. g, Per-patient estimated mean telomere length (bp) of colonies (n = 834) by age of sampling, annotated by driver status and mixed effects model regression lines and 95% confidence intervals stratified by BCR::ABL1 status. h, Per sample dot plot describing mean telomere length (bp) by clonal status (BCR::ABL1, an alternative driver mutation or ‘driverless’ clonal expansion) for PD51635, faceted by time of sampling and annotated by per sample driver status.
