Molecular mechanisms of multi-step leukemogenesis in Down syndrome

为了了解唐氏综合征白血病发生的机制，我们研究了21号染色体上的基因，并确定了ERG、RUNX1和BACH1作为候选致病基因。约10%的唐氏综合征白血病前期（TMD）发现JAK3激活突变。GATA1突变影响GATA1s蛋白的表达水平。TMD中GATA1s低突变与进展为急性巨核细胞白血病和白细胞计数降低的风险显著相关。

To understand the mechanism of leukemogensis in Down syndrome, we investigate the genes on chromosome 21 and identified ERG, RUNX1 and BACH1 as the candidates of the causative genes. JAK3 activating mutations were identified in about 10% of preleukemia (TMD) in Down syndrome. GATA1 mutations affected the expression levels of GATA1s protein. GATA1s low mutations in TMD were significantly associated with a risk of progression to acute megakaryoblastic leukemia and lower WBC counts.