{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:42Z","timestamp":1787028522043,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS via additional mutations in cohesin genes, CTCF, RAS, or JAK\/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events, and the aberrant expression of CRLF2, JAK2 mutations, and RAS pathway-activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment\u2019s role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.<\/jats:p>","DOI":"10.3390\/ijms242015325","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:55:06Z","timestamp":1697622906000},"page":"15325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hematologic Neoplasms Associated with Down Syndrome: Cellular and Molecular Heterogeneity of the Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2551-6295","authenticated-orcid":false,"given":"Edoardo","family":"Peroni","sequence":"first","affiliation":[{"name":"Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-6979","authenticated-orcid":false,"given":"Michele","family":"Gottardi","sequence":"additional","affiliation":[{"name":"Onco Hematology, Department of Oncology, Veneto Institute of Oncology, IOV-IRCCS, 31033 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8288-9784","authenticated-orcid":false,"given":"Lucia","family":"D\u2019Antona","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Mater Domini University Hospital, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7945-1864","authenticated-orcid":false,"given":"Maria Luigia","family":"Randi","sequence":"additional","affiliation":[{"name":"First Medical Clinic, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rosato","sequence":"additional","affiliation":[{"name":"Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, 35128 Padova, Italy"},{"name":"Department of Surgery Oncology and Gastroenterology, University of Padova, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-5462","authenticated-orcid":false,"given":"Giacomo","family":"Coltro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy"},{"name":"Center of Research and Innovation for Myeloproliferative Neoplasms, CRIMM, AOU Careggi, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrg.2016.154","article-title":"Down syndrome and the complexity of genome dosage imbalance","volume":"18","author":"Antonarakis","year":"2017","journal-title":"Nat. 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