MYC-stery of Down syndrome unravelled

This publication underlines, the significant findings of Sato et al., exploring novel transformative changes in preleukemic transient abnormal myelopoeisis (TAM). Findings include the identification of partial tandem duplications of RUNX1 and mutations in IRX1 and ZBTB7A, whose oncogenicity seems to involve activation of transcription factor MYC and E2F targets. As previously known, the combination of prenatal GATA1 mutations, trisomy 21, and its associated genetic imbalances, on its own results in a failure to regulate MYC and E2F pathways.This study finds that additional alterations of RUNX1, IRX1 and ZBTB7A can further drive mutagenesis of the preleukemic TAM, highlighting also therapeutic potentials in MYC-targeting strategies.

Find the commentary and according paper at:

Klusmann JH. MYC-stery of Down syndrome unraveled. Blood. 2024 Jun 20;143(25):2566-2567. doi: 10.1182/blood.2024024595. PMID: 38900477.

Sato T., et al..Landscape of driver mutations and their clinical effects on Down syndrome–related myeloid neoplasms. Blood 2024; 143 (25): 2627–2643. doi: https://doi.org/10.1182/blood.2023022247