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 Blood, 19 March 2009, Vol. 113, No. 12, pp. 2619-2628.
Prepublished online as a Blood First Edition Paper on January 12, 2009; DOI 10.1182/blood-2008-11-163501.

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Submitted November 19, 2008
Accepted December 23, 2008

Insights into the manifestations, outcomes and mechanisms of leukemogenesis in Down syndrome

Sebastien Malinge, Shai Izraeli, and John D. Crispino*

Division of Hematology/Oncology, Northwestern University, Chicago, IL, United States
Department of Pediatric Hematology and Oncology, Safra Children's Hospital and the Cancer Research Center, Tel Aviv University, Tel Hashomer, Ramat Gan, Israel

* Corresponding author; email: j-crispino{at}northwestern.edu.

Children with Down syndrome (DS) show a spectrum of clinical anomalies, including cognitive impairment, cardiac malformations and craniofacial dysmorphy. Moreover, hematologists have also noted that these children commonly show macrocytosis, abnormal platelet counts, and an increased incidence of Transient Myeloproliferative Disease (TMD), Acute Megakaryocytic Leukemia (AMKL) and Acute Lymphoid Leukemia (ALL). In this review we summarize the clinical manifestations and characteristics of these leukemias, provide an update on therapeutic strategies and patient outcomes, and discuss the most recent advances in DS-leukemia research. With the increased knowledge of the way in which trisomy 21 affects hematopoiesis and the specific genetic mutations that are found in DS-associated leukemias, we are well on our way towards designing improved strategies for treating both myeloid and lymphoid malignancies in this high risk population.


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