{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:14:46Z","timestamp":1790802886440,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent entity, occurring with unique clinical and molecular features. The presence of a long preleukemic, myelodysplastic phase, called transient abnormal myelopoiesis (TAM), precedes the initiation of ML-DS and is defined by unusual chromosomal findings. Individuals with constitutional trisomy 21 have a profound dosage imbalance in the hematopoiesis-governing genes located on chromosome 21 and thus are subject to impaired fetal as well as to neonatal erythro-megakaryopoiesis. Almost all neonates with DS develop quantitative and morphological hematological abnormalities, yet still only 5\u201310% of them present with one of the preleukemic or leukemic conditions of DS. The acquired mutations in the key hematopoietic transcription factor gene GATA1, found solely in cells trisomic for chromosome 21, are considered to be the essential step for the selective growth advantage of leukemic cells. While the majority of cases of TAM remain clinically \u2018silent\u2019 or undergo spontaneous remission, the remaining 20% to 30% of them progress into ML-DS until the age of 4 years. The hypersensitivity of ML-DS blasts to chemotherapeutic agents, including but not limited to cytarabine, and drugs\u2019 increased infectious and cardiac toxicity have necessitated the development of risk-adapted treatment protocols for children with ML-DS. Recent advances in cytogenetics and specific molecular mechanisms involved in the evolution of TAM and ML-DS are reviewed here, as well as their integration in the improvement of risk stratification and targeted management of ML-DS.<\/jats:p>","DOI":"10.3390\/cancers15133265","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T02:01:33Z","timestamp":1687312893000},"page":"3265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Myeloid Leukemia of Down Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2381-9918","authenticated-orcid":false,"given":"Aikaterini","family":"Kosmidou","sequence":"first","affiliation":[{"name":"2nd Department of Internal Medicine, General Hospital of Kavala, 65500 Kavala, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-2605","authenticated-orcid":false,"given":"Athanasios","family":"Tragiannidis","sequence":"additional","affiliation":[{"name":"2nd Department of Pediatrics, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"additional","affiliation":[{"name":"Hematology Department, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1002\/ajmg.a.33138","article-title":"Down syndrome: Comments and reflections on the 50th anniversary of Lejeune\u2019s discovery","volume":"149A","author":"Neri","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. Rev. Dis. 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