Abstract
Individuals with Down syndrome (DS) have a markedly increased risk of developing unique myeloid proliferations such as transient abnormal myelopoiesis (TAM) and myeloid leukemia associated with Down syndrome (ML-DS) [1, 2]. These proliferations occur in the first 3 years of life and are a result of several transforming genetic events that arise during the fetal and newborn period. The initial event, an additional chromosome 21, leads to increased megakaryocytic proliferation in the fetal liver. Subsequent mutation of GATA-binding protein 1 (GATA1) results in the development of TAM. Further acquisition of additional mutations of epigenetic regulators and common signaling pathways such as JAK family kinases, MPL, and multiple RAS pathway genes leads to the transformation to MS-DS [3].
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Mateos MK, Barbaric D, Byatt SA, Sutton R, Marshall GM. Down syndrome and leukemia: insights into leukemogenesis and translational targets. Transl Pediatr. 2015;4:76–92.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45:1293–9.
Cantor AB. Myeloid proliferations associated with Down syndrome. J Hematop. 2015;8:169–76.
Bhatnagar N, Nizery L, Tunstall O, Vyas P, Roberts I. Transient abnormal myelopoiesis and AML in Down syndrome: an update. Curr Hematol Malig Rep. 2016;11:333–41.
Bombery M, Vergillo J. Transient abnormal myelopoiesis in neonates: GATA get the diagnosis. Arch Pathol Lab Med. 2014;138:1302–6.
Roberts I, Alford K, Hall G, Juban G, Richmond H, Norton A, et al. Oxford-Imperial Down Syndrome Cohort Study Group. GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia. Blood. 2013;122:3908–17.
Blink M, van den Heuvel-Eibrink MM, Aalbers AM, Balgobind BV, Hollink IH, Meijerink JP, et al. High frequency of copy number alterations in myeloid leukemias of Down syndrome. Br J Haematol. 2012;158:800–3.
Blink M, Zimmermann M, von Neuhoff C, Reinhardt D, de Haas V, Hasle H, et al. Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study. Haematologica. 2014;99:299–307.
Blink M, Buitenkamp TD, van den Heuvel-Eibrink MM, Danen-van Oorschot AA, de Haas V, Reinhardt D, et al. Frequency and prognostic implications of JAK 1-3 aberrations in Down syndrome acute lymphoblastic and myeloid leukemia. Leukemia. 2011;25:1365–8.
Walters DK, Mercher T, TL G, O'Hare T, Tyner JW, Loriaux M, et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell. 2006;10:65–75.
Malinge S, Ragu C, Della-Valle V, Pisani D, Constantinescu SN, Perez C, et al. Activating mutations in human acute megakaryoblastic leukemia. Blood. 2008;112:4220–6.
Kivivuori SM, Rajantie J, Siimes MA. Peripheral blood cell counts in infants with Down’s syndrome. Clin Genet. 1996;49:15–9.
Akin K. Macrocytosis and leukopenia in Down’s syndrome. JAMA. 1988;259:842.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
McGhan, L.J., Proytcheva, M.A. (2018). Myeloid Proliferations of Down Syndrome. In: George, T., Arber, D. (eds) Atlas of Bone Marrow Pathology. Atlas of Anatomic Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7469-6_12
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7469-6_12
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-7467-2
Online ISBN: 978-1-4939-7469-6
eBook Packages: MedicineMedicine (R0)