Fig. 1: New and rare TERT_P activating variants increased promoter activity and TL investigations in malignant BM and PB cells from TERT_P-positive cases did not reveal shortening as expected.

a Schema of TERT_P with transcription factor binding sites (blue, orange, and green symbols) and new/rare TERT_P variants in myeloid malignancies (red circles). The c.1-110_1-101dup included duplication of an Sp1 binding site (green square), between nucleotides 1295095 and 1295102 (ENSG00000164362 GRCh38.p12). Adapted from Heidenreich and Kumar¹ with permission. b Relative Luciferase activity in HeLa cell line; rs refers to rs2853669 T>C. Data are shown as mean ± SD in four independent experiments. The construct with the known activating c.1-57A>C was used as an internal positive control to validate data. ***p < 0.001 vs. wild type (two sample t-test with equal variances). c Inter-individual TL analysis by Q-FISH on PHA-stimulated PB metaphases. Unique patient number (UPN) refers to Supplementary Table 2. TL is expressed as T/C%. Each dot represents the difference (ΔTL T/C%) between mean TL in each patient and each age- and sex-matched healthy control (for UPN#42 and #203: 7 males, age range 71–83, mean 78.2, median 81, and for UPN#269: 5 females, age range 64–75, mean 72, median 74). ns, not significant (one sample Student’s t test). d Intra-individual TL over time according to qPCR on  BM DNA at diagnosis and during the disease course. TL is expressed as T/S ratio. e Intra-individual TL analysis by qPCR comparing BM DNA with PB CD3⁺ cells negative for somatic mutations. TL is expressed as T/S ratio. Data are shown as mean ± SD in four independent experiments (p < 0.05, Mann–Whitney U test).