Extended Data Fig. 9: Clinical utility of the BMP-like-17 in risk stratifying non-pediatric and relapsed T-ALL patients.
(a) Selection of n = 81 young adult (age at diagnosis >= 18 years) T-ALL cases from bulk-sequenced AALL0434 cohort (n = 1335). (b) Identification of BMP-17-high cluster within AALL0434 young adult cases via Leiden clustering. n = 81 patients; n = 32 BMP-high, n = 49 BMP-low. (c) Clinical outcome comparison strategy between BMP-17-High and BMP-17-Low cases. n = 81 patients; n = 32 BMP-high, n = 49 BMP-low. (d) BMP-17 signature score in cluster 0 (BMP-high) vs clusters 1-2 (BMP-low) cases. n = 81 patients; n = 32 BMP-high, n = 49 BMP-low. (e) enrichment of EOI MRD positive and induction failure cases within BMP-High cases. n = 81 patients; n = 32 BMP-high, n = 49 BMP-low. (f) Overall (left) and event free (right) survival outcomes in BMP-High and BMP-Low cases. Cox-proportional hazard log-likelihood p-value is shown in the bottom left. n = 81 patients; n = 32 BMP-high, n = 49 BMP-low. (g-i) LASSO regression model was used to narrow the (g) BMP-17 signature, (h) BMP-surface-9 signature, and (i) BMP-119 DEG signature to the genes that were most predictive of overall survival when stratified by ETP subtype. Kaplan-Meier plots show overall survival of bulk-RNA-sequenced T-ALL patients in AALL0434 (n = 1335) and AALL1231 (n = 75) binarized using the optimized signatures. The BMP-Optimized-6 and BMP-Optimized-3 signatures were calculated using AUCell and binarized at the 50th percentile, as in Fig. 6g, h to be directly comparable. The BMP-Optimized-20 signature was computed using a z-score to positively or negatively weight genes and binarized at a z-score=0, thus directly comparable to Fig. 3m. The prognostic value of the signatures in multivariate analysis (with Day 29 MRD, CNS status, age at diagnosis, and WBC count) are shown below the Cox-proportional hazard log-likelihood p-value with Day 29 MRD as the covariate.
