The TCR-positive T-PLL cells comprise a spectrum of memory phenotypes with a predominant CM fraction and frequent unconventional patterns. (A-B) Surface (s) marker expression (flow cytometry) in PB-derived primary T-PLL cells. (A) Distribution of sTCRα/β, sCD3, sCD28 across 143 T-PLL with no case lacking all 3 receptors. (B) Spectrum of naïve/memory differentiation on the basis of expression of CD45RA, CD45RO, CCR7, and CD62L (n = 115; see supplemental Table 2 for marker-defined subsets). A 70% cutoff was used to classify the predominant differentiation. Exemplary cases (including gating strategies) for each conventional and noncanonical pattern are illustrated in supplemental Figure 1A-B. Most cases (95 of 115, 83%) had a dominant T-memory subpopulation (CD45RO⁺). Within these CD45RA⁻/RO⁺ or CD45RA⁺/RO⁺ cases, a CCR7⁺/CD62L⁺ CM pattern was most frequent. Composite cases comprised 2 distinct populations with at least 1 showing a CD45RO⁺ phenotype (12 of 115 cases, 10%). Of the few CD45RA⁺/RO⁻ cases (6 of 115, 5%), 3 (3% of total) resembled classical CCR7⁺/CD62L⁺ naïve T cells. A small number of cases had transitional phenotypes of EM-like or of terminally differentiated EM T cells with CD45RA (T-EMRA). Alignments with (co)expression of CD4 and CD8 revealed no association with CD45 isoform patterns. (C-D) Array-based GEP on 70 primary T-PLL and of healthy PB-derived naïve, pan-memory, and CM T cells (10 donors each). UMAP analysis used gene signatures identified in comparative algorithms (25 most differentially expressed genes per comparison; + fold-change sorted; P value cutoff, 0.05; supplemental Methods). The gene lists are in supplemental Table 3, and the most informative genes are illustrated in supplemental Figure 2A. For heatmaps showing signature gene expression in T-PLL vs control samples (unsupervised clustering), see supplemental Figure 2B-C. (C) UMAP on the basis of signature genes identified in the pan-memory vs naive T-cell comparison. Circles and a separator line highlight distinct clustering of healthy-donor T cells vs T-PLL cells. (D) UMAP based on signature genes identified by pan-memory vs CM T-cell comparison. (E) Clustering of 77 T-PLL vs 373 T-cell/natural killer–cell lymphomas using UMAP (5000 most differentially expressed genes over all entities). (F) Accumulation of EM T cells in TCL1A-driven murine (pre)leukemic expansions (flow cytometry). T-splenocytes from young (10 weeks) or old (10 to 16 months) Lck^pr-hTCL1A^tg mice vs age-matched C57BL/6J wild-type controls (n = 5 each). (G) Frequency-ranked TRBV gene usage in dominant TRB clonotypes of 90 T-PLL on the basis of TRB NGS.