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Clinical and biological aspects of myeloid leukemia in Down syndrome

Abstract

Children with Down syndrome are at an elevated risk of leukemia, especially myeloid leukemia (ML-DS). This malignancy is frequently preceded by transient abnormal myelopoiesis (TAM), which is self-limited expansion of fetal liver-derived megakaryocyte progenitors. An array of international studies has led to consensus in treating ML-DS with reduced-intensity chemotherapy, leading to excellent outcomes. In addition, studies performed in the past 20 years have revealed many of the genetic and epigenetic features of the tumors, including GATA1 mutations that are arguably associated with all cases of both TAM and ML-DS. Despite these advances in understanding the clinical and biological aspects of ML-DS, little is known about the mechanisms of relapse. Upon relapse, patients face a poor outcome, and there is no consensus on treatment. Future studies need to be focused on this challenging aspect of leukemia in children with DS.

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Fig. 1: Timeline of events during ML-DS progression.
Fig. 2: Clonal evolution of ML-DS and relapse.

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Acknowledgements

This review was supported in part by a grant from the NIH (CA101774 to JDC and T32CA236748 to ACB). JEF and KJC are supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA021765. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional support was provided by St. Jude /ALSAC.

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ACB, KJC, JEF, and JDC wrote the review.

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Correspondence to John D. Crispino or Jamie E. Flerlage.

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Jamie Flerlage receives research funding from Seattle Genetics. The other authors declare no conflicts of interest.

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Boucher, A.C., Caldwell, K.J., Crispino, J.D. et al. Clinical and biological aspects of myeloid leukemia in Down syndrome. Leukemia 35, 3352–3360 (2021). https://doi.org/10.1038/s41375-021-01414-y

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