ArticleCancer cell2024
Single-cell systems pharmacology identifies development-driven drug response and combination therapy in B cell acute lymphoblastic leukemia.
Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- Genomic Subtype Influences BH3 Mimetic Drug Sensitivity and Synergy with Cytotoxic Chemotherapeutics in T-cell Acute Lymphoblastic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
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- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Spatially-Resolved Multiomic Atlas of Leiomyosarcoma Identifies Two Clinically Relevant Epigenetically-Driven Cell States.bioRxiv : the preprint server for biology · 2026Article
- Cell line-specific gene network enrichment analysis for interpreting continuous phenotypes.Briefings in bioinformatics · 2026Article
- YTHDF1-ALYREF axis enhances mrna stability and tumor immune evasion in paediatric B-cell acute lymphoblastic leukemia.Functional & integrative genomics · 2026Article
- Experimentally calibrated multiscale model predicts schedule dependent drug combination effects.NPJ systems biology and applications · 2026Article
- Intra-subtype heterogeneity shapes treatment response inHemaSphere · 2026Article
- Functional precision approach in patients with very high risk acute lymphoblastic leukaemia in India: a single-centre cohort study.The Lancet regional health. Southeast Asia · 2026Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL.Science advances · 2025Article
- A Machine Learning-Based Strategy Predicts Selective and Synergistic Drug Combinations for Relapsed Acute Myeloid Leukemia.Cancer research · 2025Article
- iVAE: an interpretable representation learning framework enhances clustering performance for single-cell data.BMC biology · 2025Article
- Dual asparagine-depriving nanoparticles against solid tumors.Nature communications · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- scMINER: a mutual information-based framework for clustering and hidden driver inference from single-cell transcriptomics data.Nature communications · 2025Article
- Recent advances in the role of atypical cadherin FAT1 in tumorigenesis (Review).Oncology letters · 2025Review
- Review
- Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.Nature communications · 2025Article
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
Abstract
Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.