{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:47:25Z","timestamp":1793850445601,"version":"4.6.1"},"reference-count":49,"publisher":"American Society of Hematology","issue":"14","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 &amp;lt;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.<\/jats:p>","DOI":"10.1182\/blood.2021013442","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T11:16:02Z","timestamp":1638702962000},"page":"2198-2211","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":118,"title":["Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell\u2013like blasts in\n                    <i>KMT2A<\/i>\n                    -rearranged leukemia"],"prefix":"10.1182","volume":"139","author":[{"given":"Changya","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research and"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-2644","authenticated-orcid":false,"given":"Wenbao","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research and"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Department of Pediatrics, Perelman School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Alikarami","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0933-4707","authenticated-orcid":false,"given":"Qi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine,"},{"name":"Penn Epigenetics Institute, and"},{"name":"Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Flournoy","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine,"},{"name":"Penn Epigenetics Institute, and"},{"name":"Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Gao","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research and"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3478-3499","authenticated-orcid":false,"given":"Yasin","family":"Uzun","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research and"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5456-0255","authenticated-orcid":false,"given":"Li","family":"Fang","sequence":"additional","affiliation":[{"name":"Raymond G. 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