DYRK1A in Down syndrome: an oncogene or tumor suppressor?
Yehudit Birger, Shai Izraeli
Yehudit Birger, Shai Izraeli
Published February 22, 2012
Citation Information: J Clin Invest. 2012;122(3):807-810. https://doi.org/10.1172/JCI62372.
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Commentary

DYRK1A in Down syndrome: an oncogene or tumor suppressor?

Abstract

Children with Down syndrome (DS) have a markedly increased risk of developing acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia compared with that of children without DS. Despite recent breakthroughs, it is not clear which genes on chromosome 21, the chromosome that is trisomic in individuals with DS, cause this predisposition. In this issue of the JCI, Malinge et al. report their loss- and gain-of-function experiments in mouse and human cells that show that increased expression of the kinase encoded by the chromosome 21 gene DYRK1A suppresses the nuclear factor of activated T cells pathway and promotes AMKL. Interestingly, the same protein has been suggested to contribute to the reduced risk of epithelial cancers in adults with DS, leading to the possibility that it could be proleukemic in children and antitumorigenic in adults.

Authors

Yehudit Birger, Shai Izraeli

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Figure 1

Multistep pathogenesis of the megakaryocytic malignancies of DS.

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Multistep pathogenesis of the megakaryocytic malignancies of DS. cT21 pr...
cT21 promotes cell-autonomous fetal megakaryo-erythropoiesis. Acquired mutation of GATA1, leading to expression of GATA1s, further enhances the proliferation of these precursors and blocks terminal megakaryocytic proliferation, manifesting at birth as TMD. TMD is transient; however, in 20% of the patients, a residual submicroscopic clone acquires additional genetic abnormalities, examples of which are discussed in the main text, that lead to AMKL, which is always diagnosed before 4 years of age.