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lüll Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome Malinge S; Izraeli S; Crispino JDBlood 2009[Mar]; 113 (12): 2619-28Children 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 toward designing improved strategies for treating both myeloid and lymphoid malignancies in this high-risk population.|Animals[MESH]|Antineoplastic Combined Chemotherapy Protocols/therapeutic use[MESH]|Cell Transformation, Neoplastic/*genetics[MESH]|Chromosomes, Human, Pair 21/genetics[MESH]|Disease Models, Animal[MESH]|Disease Progression[MESH]|Down Syndrome/blood/*complications/genetics[MESH]|GATA1 Transcription Factor/genetics[MESH]|Gene Expression Regulation, Leukemic[MESH]|Genetic Predisposition to Disease[MESH]|Hematopoiesis, Extramedullary/genetics[MESH]|Humans[MESH]|Incidence[MESH]|Janus Kinases/genetics[MESH]|Leukemia, Megakaryoblastic, Acute/drug therapy/epidemiology/*etiology/genetics[MESH]|Liver/embryology/pathology[MESH]|Mice[MESH]|MicroRNAs/genetics[MESH]|Mutation[MESH]|Myeloproliferative Disorders/*congenital/drug therapy/epidemiology/etiology/genetics[MESH]|Neoplasm Proteins/genetics[MESH]|Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/epidemiology/*etiology/genetics[MESH]|Preleukemia/*congenital/drug therapy/epidemiology/etiology/genetics[MESH]|RNA, Neoplasm/genetics[MESH] |