Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.
- 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Abstract
Background
Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) patients exhibit heterogeneous responses to CD19 chimeric antigen receptor T-cell (CAR-T) therapy. However, current studies primarily focus on the CAR-T cells or the leukemia blasts, and the patient's intrinsic molecular characteristics before treatment remain poorly understood.Methods
Fifteen R/R B-ALL patients enrolled in a phase II, single-arm clinical trial (NCT04684147) were stratified at a three-month landmark into 8 good responders and 7 poor responders. Clinical characteristics, genetic alterations and pre-treatment bone marrow transcriptomics were compared between groups, and an exploratory gene-expression score was derived.Results
Differential expression and enrichment analyses identified a myeloid-like signature and upregulation of myeloid-related genes in poor responders. Seven myeloid-related genes were examined in independent patient cohorts, in B-ALL cell lines and at single-cell resolution in one patient; three were expressed by the leukemic cells themselves and four predominantly by monocytes and macrophages. A separate, variance-derived seven-gene least absolute shrinkage and selection operator (LASSO) score separated response groups in the discovery cohort (apparent area under the curve, AUC 1.00), with bias-corrected and external estimates of approximately 0.57-0.59 (external cohort AUC 0.592, 95% confidence interval 0.356-0.828).Conclusions
Pre-treatment transcriptomic profiling revealed a myeloid-like signature in R/R B-ALL patients with poor CD19 CAR-T response, warranting further investigation as a candidate correlate of treatment outcome.
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BibTeX
@article{wang2026transcriptome,
title = {{Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.}},
author = {Shisen Wang and Wenbing Liu and Ying Wang and Yingxi Xu and Haiyan Xing and Kejing Tang and Zheng Tian and Qing Rao and Shaowei Qiu and Hui Wei and Runxia Gu and Min Wang and Jianxiang Wang},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72395},
url = {https://europepmc.org/article/MED/42897095},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Transcriptome Analysis Identifies a Myeloid-Like Signature in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Poor Response to CD19 Chimeric Antigen Receptor T Cell Therapy.
AU - Shisen Wang
AU - Wenbing Liu
AU - Ying Wang
AU - Yingxi Xu
AU - Haiyan Xing
AU - Kejing Tang
AU - Zheng Tian
AU - Qing Rao
AU - Shaowei Qiu
AU - Hui Wei
AU - Runxia Gu
AU - Min Wang
AU - Jianxiang Wang
PY - 2026
DA - 2026/10/01
JO - Cancer medicine
DO - 10.1002/cam4.72395
UR - https://europepmc.org/article/MED/42897095
AB - Background Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) patients exhibit heterogeneous responses to CD19 chimeric antigen receptor T-cell (CAR-T) therapy. However, current studies primarily focus on the CAR-T cells or the leukemia blasts, and the patient's intrinsic molecular characteristics before treatment remain poorly understood.Methods Fifteen R/R B-ALL patients enrolled in a phase II, single-arm clinical trial (NCT04684147) were stratified at a three-month landmark into 8 good responders and 7 poor responders. Clinical characteristics, genetic alterations and pre-treatment bone marrow transcriptomics were compared between groups, and an exploratory gene-expression score was derived.Results Differential expression and enrichment analyses identified a myeloid-like signature and upregulation of myeloid-related genes in poor responders. Seven myeloid-related genes were examined in independent patient cohorts, in B-ALL cell lines and at single-cell resolution in one patient; three were expressed by the leukemic cells themselves and four predominantly by monocytes and macrophages. A separate, variance-derived seven-gene least absolute shrinkage and selection operator (LASSO) score separated response groups in the discovery cohort (apparent area under the curve, AUC 1.00), with bias-corrected and external estimates of approximately 0.57-0.59 (external cohort AUC 0.592, 95% confidence interval 0.356-0.828).Conclusions Pre-treatment transcriptomic profiling revealed a myeloid-like signature in R/R B-ALL patients with poor CD19 CAR-T response, warranting further investigation as a candidate correlate of treatment outcome.
SN - 2045-7634
ER -