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The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome

Abstract

Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). Although the etiology of this higher risk of developing leukemia remains largely unclear, the recent identification of CRLF2 (cytokine receptor like factor 2) and JAK2 mutations and study of the effect of trisomy of Hmgn1 and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A) on B-cell development have shed significant new light on the disease process. Here we focus on the clinical features, biology and genetics of ALL in children with DS. We review the unique characteristics of DS-ALL on both the clinical and molecular levels and discuss the differences in treatments and outcomes in ALL in children with DS compared with those without DS. The identification of new biological insights is expected to pave the way for novel targeted therapies.

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Acknowledgements

This review was supported by grants from the National Institutes of Health (R01 CA101774, to JC), the Rally and Bear Necessities Foundations (to JC), the Unites States–Israel Binational Science Foundation (to SI and JC), the Samuel Waxman Cancer Research Foundation (to SI and JC), the Israel Science Foundation Legacy Program (to SI), the Israel Cancer Research Foundation (to SI) and Children with Cancer UK (to SI). This review is also supported, in part, by an Alpha Omega Alpha Carolyn L Kuckein Student Research Fellowship.

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Dr Hijiya is a consultant for Novartis. The other authors declare no conflict of interest.

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Lee, P., Bhansali, R., Izraeli, S. et al. The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome. Leukemia 30, 1816–1823 (2016). https://doi.org/10.1038/leu.2016.164

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