AI Article Synopsis
- Transient abnormal myelopoiesis (TAM) primarily affects infants with Down syndrome and can sometimes progress to a more serious condition known as Down syndrome-related acute megakaryoblastic leukemia (DS-AMKL).
- TAM is usually self-limiting and is associated with GATA1 mutations and trisomy 21, the extra chromosome present in Down syndrome.
- Genomic analysis shows that DS-AMKL develops from TAM due to further mutations in various genes and pathways, indicating a complex evolution from a pre-existing condition.
Article Abstract
Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome-related myeloid disorders is poorly understood, except for GATA1 mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single GATA1 mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%), CTCF (20%), and EZH2, KANSL1 and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases, MPL, SH2B3 (LNK) and multiple RAS pathway genes (47%).
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| http://dx.doi.org/10.1038/ng.2759 | DOI Listing |
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