Figure S1.
LOUCY and CUTLL3 cell lines are models of the high-risk BMP-like subtype of ETP-ALLs. (A–C) Immunophenotype of LOUCY cells (A), CUTLL3 cells (B), and THP-6 cells (C) using ETP-ALL criteria (Coustan-Smith et al., 2009). (D) Transcriptome similarity of 17 T-ALL cell lines with BM and T-cell developmental subsets identified in scRNA-seq data (Lasry et al., 2023; Park et al., 2020). Pearson correlation was calculated for over 901 lineage-determinant genes. Row-based Z-score normalized correlations and hierarchical clustering are shown. Cell states with maximum correlation to LOUCY and CUTLL3 are boxed. (E) Microarray expression of ETP-TF5 genes in CD34+ cord blood cells and human thymocyte subsets (GSE22601). (F) Averaged expression of ETP-TF5 genes in day 29 MRD-negative and day 29 MRD-positive ETP/near-ETP T-ALL blasts in TARGET. ETP-TF5 factors (MEF2C, LYL1, HHEX, MYCN, and LMO2) are BMP-like transcription factors (Fig. 1 F) that were experimentally found to be ETP-ALL drivers (Cante-Barrett et al., 2022; Homminga et al., 2011; León et al., 2020; McCormack et al., 2010, 2013; Smith et al., 2014; Treanor et al., 2013). (G) ETP-TF5 signature score within n = 1,141 immunophenotyped AALL0434 patients profiled using bulk RNA-seq (Pölönen et al., 2024). P values from two-sided Mann–Whitney test are shown. (H) ETP-TF5 signature score (AUCell) in BMP-like and T-specified T-ALL blasts obtained from scRNA-seq on 40 cases from AALL0434; 10,000 cells per group (Xu et al., 2024). P values from two-sided Mann-Whitney test are shown. (I) Kaplan–Meier plot showing overall survival of bulk RNA-seq ETP-ALL patients in AALL0434 binarized using the ETP-TF5 signature. Prognostic values of the signatures in multivariate analysis controlling for day 29 MRD is shown below the Cox-proportional hazard coefficient P value controlling for day 29 MRD, day 29 CNS disease, age, and peripheral WBC count at diagnosis (note: only day 29 MRD > day 29 CNS status were prognostic in the full AALL0434 cohort). (J) Identification of LOUCY and CUTLL3 cell lines as experimental models of high-risk ETP-ALL using the ETP-TF5 signature; n = 17. DepMap 22Q4, GSE138659, GSE59810, and GSE164928. (K) qPCR analysis of averaged expression of ETP-TF5 genes normalized to mature T-ALL reference (Jurkat cells, set to 1). BMP-like cells were experimentally defined as expressing the ETP-TF5 signature at >30-fold higher levels than Jurkat cells. (L) qRT-PCR for ZMIZ1 expression in PDX1 and PDX2 upon transduction with ZMIZ1 shRNA; n = 3/group. P values were based one-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Refer to the image caption for details.

LOUCY and CUTLL3 cell lines are models of the high-risk BMP-like subtype of ETP-ALLs. (A–C) Immunophenotype of LOUCY cells (A), CUTLL3 cells (B), and THP-6 cells (C) using ETP-ALL criteria (Coustan-Smith et al., 2009). (D) Transcriptome similarity of 17 T-ALL cell lines with BM and T-cell developmental subsets identified in scRNA-seq data (Lasry et al., 2023; Park et al., 2020). Pearson correlation was calculated for over 901 lineage-determinant genes. Row-based Z-score normalized correlations and hierarchical clustering are shown. Cell states with maximum correlation to LOUCY and CUTLL3 are boxed. (E) Microarray expression of ETP-TF5 genes in CD34+ cord blood cells and human thymocyte subsets (GSE22601). (F) Averaged expression of ETP-TF5 genes in day 29 MRD-negative and day 29 MRD-positive ETP/near-ETP T-ALL blasts in TARGET. ETP-TF5 factors (MEF2C, LYL1, HHEX, MYCN, and LMO2) are BMP-like transcription factors (Fig. 1 F) that were experimentally found to be ETP-ALL drivers (Cante-Barrett et al., 2022; Homminga et al., 2011; León et al., 2020; McCormack et al., 2010, 2013; Smith et al., 2014; Treanor et al., 2013). (G) ETP-TF5 signature score within n = 1,141 immunophenotyped AALL0434 patients profiled using bulk RNA-seq (Pölönen et al., 2024). P values from two-sided Mann–Whitney test are shown. (H) ETP-TF5 signature score (AUCell) in BMP-like and T-specified T-ALL blasts obtained from scRNA-seq on 40 cases from AALL0434; 10,000 cells per group (Xu et al., 2024). P values from two-sided Mann-Whitney test are shown. (I) Kaplan–Meier plot showing overall survival of bulk RNA-seq ETP-ALL patients in AALL0434 binarized using the ETP-TF5 signature. Prognostic values of the signatures in multivariate analysis controlling for day 29 MRD is shown below the Cox-proportional hazard coefficient P value controlling for day 29 MRD, day 29 CNS disease, age, and peripheral WBC count at diagnosis (note: only day 29 MRD > day 29 CNS status were prognostic in the full AALL0434 cohort). (J) Identification of LOUCY and CUTLL3 cell lines as experimental models of high-risk ETP-ALL using the ETP-TF5 signature; n = 17. DepMap 22Q4, GSE138659, GSE59810, and GSE164928. (K) qPCR analysis of averaged expression of ETP-TF5 genes normalized to mature T-ALL reference (Jurkat cells, set to 1). BMP-like cells were experimentally defined as expressing the ETP-TF5 signature at >30-fold higher levels than Jurkat cells. (L) qRT-PCR for ZMIZ1 expression in PDX1 and PDX2 upon transduction with ZMIZ1 shRNA; n = 3/group. P values were based one-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal