Fig. 3: Enhanced MYC target expression is associated with T-PLL progression.
A Mean expression scores of the HALLMARK MYC targets V1 gene set34. Upregulation from indolent to active T-PLL was observed in 9/11 patients (p = 0.0139, permutation test, B = 10,000, two-sided). B Mean HALLMARK MYC targets V1 expression scores of shrinking and expanding T-PLL cell clusters (****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, MWW, two-sided). C Increase of MYC mRNA expression during T-PLL development. Left: Cell-based expression levels of MYC mRNA in healthy-donor derived T cells73, indolent-stage, and active-stage T-PLL cells. Right: Scaled mean MYC mRNA expression in shrinking (n = 172) vs expanding (n = 216) T-PLL cell clusters (p < 0.0001, MWW, two-sided). D Significant upregulation of MYC in two independent T-PLL data sets (each p < 0.0001, MWW, two-sided, left: gene expression array data of 69 T-PLL compared to CD3 + T cells of 10 healthy donors13, right: mRNA sequencing of 48 T-PLL and CD3 + T cells of 6 healthy donors35). E Relative distribution of inferred MYC copy number states in T-PLL cells. 7/11 T-PLL pairs (63.6%) presented an increase of MYC copy number-elevated T-PLL cells from indolent to active disease. (I: indolent, A: active) F Significant correlation of MYC mRNA expression and HALLMARK MYC targets V2 expression scores in n = 1000 T-PLL cell pseudo-bulks (p < 0.0001, r = 0.945, Pearson correlation, two-sided, gray band: 95% confidence interval). G Western blot of MYC protein expression in age-matched healthy-donor derived T cells (n = 4, gray line), indolent (n = 5, blue line), and active T-PLL (n = 5, red line). H Densitometrically quantified MYC protein expression from (G). Upregulated MYC protein expression in indolent (p = 0.032, MWW, two-sided) and active-stage T-PLL cells (p = 0.064, MWW, two-sided) compared to healthy-donor derived T cells. *PBMCs were collected not from the original sample at diagnosis, but shortly thereafter. I Correlation of MYC protein levels to mean HALLMARK MYC target gene expression scores (MYC targets V1: rho=0.8, p = 0.133; MYC targets V2: rho=0.9, p = 0.083, Spearman correlation, two-sided). J Mean HALLMARK MYC targets V2 gene expression scores correlated to mean expression scores of energy metabolism gene sets in shrinking and expanding T-PLL clusters (HALLMARK oxidative phosphorylation: rho=0.728, p < 0.0001; HALLMARK glycolysis: rho=0.697, p < 0.0001, Spearman correlation, two-sided). Gray band: 95% confidence interval. Definition of box plots: center: 50th percentile, box bounds: 25th and 75th percentiles (IQR), whiskers: smallest and largest observations (A) within 1.5×IQR of the box (B–D, H). Source data and complete summaries of statistical analyses are provided in the Source Data file.
