ArticleBlood2022
Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell-like blasts in KMT2A-rearranged leukemia.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed.
- Lineage switch in leukemia and lymphoma: case reports and molecular and cellular mechanisms.Blood neoplasia · 2026Review
- Plasticity under pressure: biology and detection of lineage switch in acute leukemia.Leukemia · 2026Review
- Interpretable multi-omics integration across mixed-order tensors with MANTRA.Molecular systems biology · 2026Article
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- Epigenetics as a mechanism of lineage extinction and relapse of B-cell lymphoma treated with CD19 CAR T-cell therapy.Blood neoplasia · 2026Article
- Developmental timing distinguishes pediatric and adult cancers through retention and rewiring mechanisms.Nature communications · 2026Review
- A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.Cell reports. Medicine · 2026Article
- SCOTCH: isoform-level characterization of gene expression through long-read single-cell RNA sequencing.Nature communications · 2026Article
- GatorSC: multi-scale cell and gene graphs with mixture-of-experts fusion for single-cell transcriptomics.Briefings in bioinformatics · 2026Article
- CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples.Molecular cell · 2026Article
- Single-cell multiomic atlas of healthy pediatric bone marrow reveals age-dependent differences in lineage differentiation driven by stromal signaling.Nature immunology · 2026Article
- A practical guide to targeted single-cell RNA sequencing technologies.Communications biology · 2026Review
- HSCs/MPPs as cells of origin with altered differentiation hierarchy impairing immunomicroenvironment inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intra-subtype heterogeneity shapes treatment response inHemaSphere · 2026Article
- CD19-negative relapse after CAR-T cell therapy: mechanisms of antigen escape and lineage switch.Frontiers in immunology · 2026Review
- KMT2A-Mediated transcriptional regulation in stemness and cancer: molecular mechanisms and therapeutic opportunities.Medical oncology (Northwood, London, England) · 2025Review
- RoCK and ROI: single-cell transcriptomics with multiplexed enrichment of selected transcripts and region-specific sequencing.Nature communications · 2025Article
- GatorSC: Multi-Scale Cell and Gene Graphs with Mixture-of-Experts Fusion for Single-Cell Transcriptomics.bioRxiv : the preprint server for biology · 2025Article
- Systematic Evaluation of GAPs and GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies.Cancer discovery · 2025Article
- Genes-first and phenotypes-first paths to treatment resistance in hematological malignancies.Cell death & disease · 2025Review
10 more citing papers are in PubMed but not listed here.
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25 authors.
Funding
Abstract
KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single-cell multiomics analyses. We uncovered the following critical new insights: leukemia cells from patients <6 months have significantly increased lineage plasticity. Steroid response pathways are downregulated in the most immature blasts from younger patients. We identify a hematopoietic stem and progenitor-like (HSPC-like) population in the blood of younger patients that contains leukemic blasts and form an immunosuppressive signaling circuit with cytotoxic lymphocytes. These observations offer a compelling explanation for the ability of leukemias in young patients to evade chemotherapy and immune-mediated control. Our analysis also revealed preexisting lymphomyeloid primed progenitors and myeloid blasts at initial diagnosis of B-ALL. Tracking of leukemic clones in 2 patients whose leukemia underwent a lineage switch documented the evolution of such clones into frank acute myeloid leukemia (AML). These findings provide critical insights into KMT2A-r ALL and have clinical implications for molecularly targeted and immunotherapy approaches. Beyond infant ALL, our study demonstrates the power of single-cell multiomics to detect tumor intrinsic and extrinsic factors affecting rare but critical subpopulations within a malignant population that ultimately determines patient outcome.
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