Extended Data Fig. 10. Imetelstat response classification in AML PDX.
a, Imetelstat response classification: AML burden quantified as peripheral blood donor chimerism per day and spleen weights from imetelstat vs. vehicle control-treated PDX by imetelstat response group. N = 84 (sustained responders per treatment group each); n = 48 (intermediate or poor responders per treatment group each). Solid lines represent the median from each group ± 95% confidence interval. Statistics based on unpaired two-sided t-test on log-transformed data: P = 1.32 × 10−11 (PB AML burden in sustained responders: PBS vs. imetelstat), P = 6.68 × 10−3 (PB AML burden in intermediate responders: PBS vs. imetelstat), P = 8.82 × 10−5 (spleen weight in sustained responders: PBS vs. imetelstat), P = 1.34 × 10−2 (spleen weight in interdediate responders: PBS vs. imetelstat), P = 2.8 × 10−2 (spleen weight in poor responders: PBS vs. imetelstat). b-h, Representation of clinical and molecular parameters in AML patient samples either characterized as sustained, intermediate, or poor responders to imetelstat: ELN2017 risk (b), cytogenetics (c), WHO disease classification (d), gender (e), AML patient age at sampling (f), FLT3-ITD allelic ratio (g), and TERT mRNA expression levels at baseline from RNA-seq analysis (h). Results were not statistically different (that is according to two-tailed Fisher’s exact test for b-e; one-way-ANOVA for f-h). N = 14 sustained, n = 8 intermediate, n = 8 poor responders to imetelstat. i, AML burden in imetelstat-treated normalized to vehicle control-treated PDX in relation to NRAS mutational status: NRAS wild-type (wt; n = 144), mutant NRAS (mut; n = 36). Simple linear regression indicates the slope being significantly different from 0 with p = 8.8 × 10−3. j, Telomeric restriction fragment analysis of genomic DNA isolated from viable AML patient cells at baseline from all 30 individual AML patient samples included in the preclinical trial of imetelstat in AML PDX.