Fig. 6: A consensus 17-gene BMP-like signature predicts OS across all subtypes of T-ALL.
a, Arrest states of leukemic cells from CR (n = 6) and MRD-positive (n = 4) participants with non-ETP-ALL based on projection to healthy scRNA-seq (left) and scATAC-seq (right) reference trajectory. b, Proportion of non-ETP blasts in precommitment (pre-commit, all cells before the pre-T cell stage) and postcommitment (post-commit, after the pre-T cell stage) developmental arrest state. P values from a two-sided Mann–Whitney test are indicated (n = 68,801 cells; total cells: CR, 52,971; MRD-positive, 15,830; precomitted blasts: CR, 7,152; MRD-positive, 11,047). c, Arrest states of precommitted non-ETP blasts in CR (n = 6) and MRD-positive (n = 4) participants. BMP-like encapsulates all cells that possess multipotent potential (HSPC, LMPP, CLP or ETP). d, Kaplan–Meier plot showing OS of participants with non-ETP-ALL in AALL0434 when binarized using signatures (sig) derived from precommitted non-ETP blasts and BMP-like non-ETP blasts. The P value for the log-likelihood statistic of a Cox proportional hazard test with day 29 MRD as a covariate is shown to the bottom left. e, Overlap of ETP BMP-like and non-ETP BMP-like DEGs to create consensus signature for risk stratification in AALL0434 (fully sequenced) and AALL1231 (partially sequenced). BMP-like DEGs were filtered for mean log2 fold change (FC) > 0.9 between ETP and non-ETP comparisons. f, Expression score of BMP-17 signature score and BMP-17 marker genes within bone marrow and thymus scRNA-seq reference (n = 49,623 cells). Multipotent BMP populations with high BMP-17 expression are circled. g,h, Kaplan–Meier plot showing OS of bulk RNA-seq participants with T-ALL in AALL0434 (n = 1,335 participants) and AALL1231 (n = 75 participants) binarized using the BMP-17 signature. The prognostic value of the BMP-17 signature in multivariate analysis (with day 29 MRD, CNS status, WBC count and age at diagnosis) is shown below the Cox proportional hazard log-likelihood P value with day 29 MRD as covariate. i,j, Change in BMP-like and T-specified signature scores in AALL0434 diagnosis and relapse sample pairs (n = 27: near-ETP, 4; non-ETP, 23). P values from a two-sided paired t-test are shown. The box includes the median, hinges mark the 25th and 75th percentiles and whiskers extend 1.5× the interquartile range.
