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Transient abnormal myelopoiesis/acute megakaryoblastic leukemia diagnosed in the placenta of a stillborn Down syndrome fetus with targeted next-generation sequencing

Leukemia volume 29, pages 232–233 (2015)Cite this article

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The risk to develop leukemia is increased in individuals with Down syndrome.1 According to the WHO classification, transient abnormal myelopoiesis (TAM) is a unique preleukemic disorder of Down syndrome newborns with clinical and morphological findings indistinguishable from acute myeloid leukemia (AML).2 In the majority of cases the patients are nearly asymptomatic apart from the presence of blasts of megakaryocytic lineage, and achieve spontaneous remission within the first 3 months.3 In neonates with Down syndrome TAM occurs in ~10% of patients, with the potential to transform into AML, usually with megakaryoblastic differentiation (AKML).4

We analyzed the placenta of a 33-year-old woman (gravida 1, para 1) in the 24th week of gestation with a stillborn male fetus with known trisomy 21 diagnosed by amniocentesis. Ultrasound testing 3 weeks previously had shown a severe malformation syndrome and beginning of hydrops fetalis. An autopsy of the fetus was not granted.

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References

  1. Hasle H, Clemmensen IH, Mikkelsen M . Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet 2000; 355: 165–169.

    Article  CAS  PubMed  Google Scholar 

  2. Baumann I, Niemeyer CM, Brunning RD, Arber DA, Porwit A . Myeloid proliferations in Down syndrome. In: Swerdlow SH, Campo E, Harris NL et al (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues IARC: Lyon, France, 2008, pp142–144.

    Google Scholar 

  3. Roizen NJ, Patterson D . Down's syndrome. Lancet 2003; 361: 1281–1289.

    Article  PubMed  Google Scholar 

  4. Zipursky A . Transient leukaemia—a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol 2003; 120: 930–938.

    Article  PubMed  Google Scholar 

  5. Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A . GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood 2003; 101: 4301–4304.

    Article  CAS  PubMed  Google Scholar 

  6. Hoeller S, Bihl MP, Tzankov A, Chaffard R, Hirschmann P, Miny P et al. Morphologic and GATA1 sequencing analysis of hematopoiesis in fetuses with trisomy 21. Hum Pathol 2014; 45: 1003–1009.

    Article  CAS  PubMed  Google Scholar 

  7. Roberts I, Alford K, Hall G, Juban G, Richmond H, Norton A et al. GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia. Blood 2013; 122: 3908–3917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hasle H, Abrahamsson J, Arola M, Karow A, O'Marcaigh A, Reinhardt D et al. Myeloid leukemia in children 4 years or older with Down syndrome often lacks GATA1 mutation and cytogenetics and risk of relapse are more akin to sporadic AML. Leukemia 2008; 22: 1428–1430.

    Article  CAS  PubMed  Google Scholar 

  9. Klusmann JH, Creutzig U, Zimmermann M, Dworzak M, Jorch N, Langebrake C et al. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood 2008; 111: 2991–2998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rankin J, Tennant PW, Bythell M, Pearce MS . Predictors of survival in children born with Down syndrome: a registry-based study. Pediatrics 2012; 129: e1373–e1381.

    Article  PubMed  Google Scholar 

  11. Robertson M, De Jong G, Mansvelt E . Prenatal diagnosis of congenital leukemia in a fetus at 25 weeks' gestation with Down syndrome: case report and review of the literature. Ultrasound Obstet Gynaecol 2003; 21: 486–489.

    Article  CAS  Google Scholar 

  12. Heald B, Hilden JM, Zbuk K, Norton A, Vyas P, Theil KS et al. Severe TMD/AMKL with GATA1 mutation in a stillborn fetus with Down syndrome. Nat Clin Pract Oncol 2007; 4: 433–438.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Pathology and Neuropathology, Comprehensive Cancer Center and University Hospital Tuebingen, Tuebingen, Germany

    B Federmann, S Haen & F Fend

  2. MLL Munich Leukemia Laboratory, Munich, Germany

    A Fasan

  3. Department of Obstetrics and Gynaecology, Comprehensive Cancer Center and University Hospital Tuebingen, Tuebingen, Germany

    K O Kagan

Authors
  1. B Federmann
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  2. A Fasan
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  3. K O Kagan
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  4. S Haen
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  5. F Fend
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Corresponding author

Correspondence to F Fend.

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The authors declare no conflict of interest.

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Federmann, B., Fasan, A., Kagan, K. et al. Transient abnormal myelopoiesis/acute megakaryoblastic leukemia diagnosed in the placenta of a stillborn Down syndrome fetus with targeted next-generation sequencing. Leukemia 29, 232–233 (2015). https://doi.org/10.1038/leu.2014.258

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