Spontaneously regressed CLL tumors exhibit a distinct transcriptomic profile. RNA-seq was carried out on sorted CD19⁺CD5⁺ CLL cells from subjects with spontaneous CLL regression (n = 15, from the regression time point), indolent M-CLL (n = 16), progressive M-CLL (n = 8) and UM-CLL (n = 8), or on isolated B cells from healthy donors (n = 3). (A) Gene-expression profiles of spontaneously (Spon) regressed tumors were compared against that of age-matched indolent M-CLL tumors, by 1-way ANOVA with Tukey post hoc analysis. Hierarchical clustering analysis demonstrates differential gene expression between spontaneously regressed and indolent M-CLL. (B) Gene set enrichment analysis (GSEA) showing differential expression of MYC and Myc target genes in spontaneously regressed vs indolent M-CLL tumors. (C) Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis showing enrichment of biological processes in spontaneously regressed CLL relative to indolent M-CLL. Biological processes that are upregulated in spontaneously regressed CLL are indicated in red, whereas those that are downregulated in these tumors are indicated in blue. (D) Multidimensional principal component analysis (PCA) of all samples by partial least squares discrimination (PLS-DA) showing distinct clustering of spontaneous regression cases. (E) Unsupervised hierarchical clustering analysis of all samples showing clustering of spontaneous regression cases overlapping with indolent M-CLL cases. rRNA, ribosomal RNA; SRP, signal-recognition particle.