Editing Down syndrome (section)

==== Blood cancers ====
[[Leukemia]] is 10 to 15 times more common in children with Down syndrome.<ref name=Hick2012/> In particular, [[acute lymphoblastic leukemia]] is 20 times more common and the megakaryoblastic form of [[acute myeloid leukemia]] ([[acute megakaryoblastic leukemia]]), is 500 times more common.<ref name="pmid22867885"/> Acute megakaryoblastic leukemia (AMKL) is a leukemia of [[megakaryoblast]]s, the precursors cells to [[megakaryocyte]]s which form blood [[platelet]]s.<ref name="pmid22867885">{{cite journal | vauthors = Seewald L, Taub JW, Maloney KW, McCabe ER | title = Acute leukemias in children with Down syndrome | journal = Molecular Genetics and Metabolism | volume = 107 | issue = 1–2 | pages = 25–30 | date = September 2012 | pmid = 22867885 | doi = 10.1016/j.ymgme.2012.07.011 }}</ref> Acute lymphoblastic leukemia in Down syndrome accounts for 1–3% of all childhood cases of ALL. It occurs most often in those older than nine years or having a [[white blood cell count]] greater than 50,000 per [[microliter]] and is rare in those younger than one year old. ALL in Down syndrome tends to have poorer outcomes than other cases of ALL in people without Down syndrome.<ref name="pmid22867885"/><ref name="pmid27285583">{{cite journal | vauthors = Lee P, Bhansali R, Izraeli S, Hijiya N, Crispino JD | title = The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome | journal = Leukemia | volume = 30 | issue = 9 | pages = 1816–1823 | date = September 2016 | pmid = 27285583 | pmc = 5434972 | doi = 10.1038/leu.2016.164 }}</ref>  In short, the likelihood of developing acute myeloid leukemia (AML) and [[acute lymphoblastic leukemia]] (ALL) is higher in children with Down syndrome compared to those without Down syndrome.<ref>{{cite journal | vauthors = Li J, Kalev-Zylinska ML | title = Advances in molecular characterization of myeloid proliferations associated with Down syndrome | journal = Frontiers in Genetics | volume = 13 | pages = 891214 | date = 2022 | pmid = 36035173 | pmc = 9399805 | doi = 10.3389/fgene.2022.891214 | doi-access = free }}</ref>

[[Myeloid leukemia]] typically precedes Down syndrome and is accompanied by a condition known as [[Transient myeloproliferative disease|transient abnormal myelopoiesis]] (TAM), which generally disrupts the differentiation of megakaryocytes and erythrocytes.<ref name="The paradox of Myeloid Leukemia ass">{{cite journal | vauthors = Gupte A, Al-Antary ET, Edwards H, Ravindranath Y, Ge Y, Taub JW | title = The paradox of Myeloid Leukemia associated with Down syndrome | journal = Biochemical Pharmacology | volume = 201 | pages = 115046 | date = July 2022 | pmid = 35483417 | doi = 10.1016/j.bcp.2022.115046 | s2cid = 248431139 }}</ref> In Down syndrome, AMKL is typically preceded by [[transient myeloproliferative disease]] (TMD), a disorder of [[Haematopoiesis|blood cell production]] in which non-cancerous megakaryoblasts with a mutation in the ''[[GATA1]]'' gene rapidly divide during the later period of pregnancy.<ref name="pmid22867885"/><ref name="pmid25956670">{{cite journal | vauthors = Tamblyn JA, Norton A, Spurgeon L, Donovan V, Bedford Russell A, Bonnici J, Perkins K, Vyas P, Roberts I, Kilby MD | display-authors = 6 | title = Prenatal therapy in transient abnormal myelopoiesis: a systematic review | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 101 | issue = 1 | pages = F67–F71 | date = January 2016 | pmid = 25956670 | doi = 10.1136/archdischild-2014-308004 | s2cid = 5958598 | url = https://ora.ox.ac.uk/objects/uuid:73db9b1c-e082-43bc-91a5-db03b26d18d3 }}</ref> GATA1 mutations combined with trisomy 21 contribute to a predisposition to TAM.<ref name="pmid27510823"/> In trisomy 21, the process of leukemogenesis starts in early fetal life, with genetic factors, including GATA1 mutations, contributing to the development of TAM on the preleukemic pathway.<ref name="The paradox of Myeloid Leukemia ass"/> The condition affects 3–10% of babies with Down.<ref name="pmid22867885"/> While it often spontaneously resolves within three months of birth, it can cause serious blood, liver, or other complications.<ref name=Gam2012>{{cite journal | vauthors = Gamis AS, Smith FO | title = Transient myeloproliferative disorder in children with Down syndrome: clarity to this enigmatic disorder | journal = British Journal of Haematology | volume = 159 | issue = 3 | pages = 277–287 | date = November 2012 | pmid = 22966823 | doi = 10.1111/bjh.12041 | s2cid = 37593917 | doi-access = free }}</ref> In about 10% of cases, TMD progresses to AMKL during the three months to five years following its resolution.<ref name="pmid22867885"/><ref name=Gam2012/><ref name="pmid27510823">{{cite journal | vauthors = Bhatnagar N, Nizery L, Tunstall O, Vyas P, Roberts I | title = Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update | journal = Current Hematologic Malignancy Reports | volume = 11 | issue = 5 | pages = 333–341 | date = October 2016 | pmid = 27510823 | pmc = 5031718 | doi = 10.1007/s11899-016-0338-x }}</ref>