A transcriptional signal associated with mesenchymal stromal cells predicts overall survival in B cell acute lymphoblastic leukemia
Abstract
The bone marrow microenvironment influences leukemic behavior in B-cell acute lymphoblastic leukemia (B-ALL), but clinically relevant MSC-associated transcriptional signals remain poorly defined. We derived a lineage-specific mesenchymal stromal cell (MSC) signature from a normal bone marrow single-cell RNA-sequencing reference and evaluated it in bulk transcriptomes from 56 newly diagnosed patients with B-ALL. The 35-gene signature formed two co-expression modules. The turquoise module, but not the blue module, was associated with inferior overall survival and distinct exploratory metabolic and immune-related patterns. We then developed a 10-gene-pair model from turquoise-associated genes. The model stratified survival in the derivation cohort and retained prognostic value in the external TARGET cohort using the same cutoff. In multivariable TARGET analysis, the model remained an adverse prognostic factor after adjustment for age, white blood cell count, and day 29 minimal residual disease. Exploratory analyses also identified distinct predicted drug-sensitivity associations. These findings indicate that a single-cell-informed MSC-associated transcriptional signal can support prognostic modeling, while the cellular source of this signal requires orthogonal validation.
Related
- Epithelial–mesenchymal plasticity is associated with transcriptional variation in regulated cell death and immune signaling programs in lung adenocarcinoma
- Diabetes Mellitus Independently Predicts Survival in Beta-Lactam-Associated Hypokalemia
- PODXL2 Expression Is Associated with Inferior Survival, Adverse-Risk Features, and Distinct Transcriptional Programs in Acute Myeloid Leukemia
- A novel prognostic model based on CD8+T cell infiltration-associated differentially expressed genes and immune-related genes predicts survival in bladder cancer
- Age-stratified survival and competing mortality in adult acute lymphoblastic leukemia and lymphoblastic lymphoma: a population-based competing-risk and restricted mean survival analysis
BibTeX
@article{li2026transcriptional,
title = {{A transcriptional signal associated with mesenchymal stromal cells predicts overall survival in B cell acute lymphoblastic leukemia}},
author = {Xindi Li and Shicong Zhu and Zhitao Wang and Hongkai Zhu and Cheng Xing and Zhihua Wang},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-77851-5},
url = {https://www.nature.com/articles/s41598-026-77851-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A transcriptional signal associated with mesenchymal stromal cells predicts overall survival in B cell acute lymphoblastic leukemia
AU - Xindi Li
AU - Shicong Zhu
AU - Zhitao Wang
AU - Hongkai Zhu
AU - Cheng Xing
AU - Zhihua Wang
PY - 2026
DA - 2026/10/28
JO - Scientific Reports
DO - 10.1038/s41598-026-77851-5
UR - https://www.nature.com/articles/s41598-026-77851-5
AB - The bone marrow microenvironment influences leukemic behavior in B-cell acute lymphoblastic leukemia (B-ALL), but clinically relevant MSC-associated transcriptional signals remain poorly defined. We derived a lineage-specific mesenchymal stromal cell (MSC) signature from a normal bone marrow single-cell RNA-sequencing reference and evaluated it in bulk transcriptomes from 56 newly diagnosed patients with B-ALL. The 35-gene signature formed two co-expression modules. The turquoise module, but not the blue module, was associated with inferior overall survival and distinct exploratory metabolic and immune-related patterns. We then developed a 10-gene-pair model from turquoise-associated genes. The model stratified survival in the derivation cohort and retained prognostic value in the external TARGET cohort using the same cutoff. In multivariable TARGET analysis, the model remained an adverse prognostic factor after adjustment for age, white blood cell count, and day 29 minimal residual disease. Exploratory analyses also identified distinct predicted drug-sensitivity associations. These findings indicate that a single-cell-informed MSC-associated transcriptional signal can support prognostic modeling, while the cellular source of this signal requires orthogonal validation.
SN - 2045-2322
ER -