Correction of Hematopoietic Defects in Down Syndrome by Chromosome 21 Silencing
This project will capitalize upon and extend a highly innovative means to study and advance the treatment of hematological complications of Down syndrome, based on the ability to "silence" (i.e. turn off) the extra copy of chromosome 21 that causes this disorder. Down syndrome is a common congenital disorder in which children have a greatly increased risk of blood abnormalities, including a myeloproliferative disorder and leukemia. Understanding abnormal blood formation in Down syndrome is important for the development of treatments, and is relevant to understanding the basis for blood disorders in children more generally.
We will use a novel method to directly compare human Down syndrome cells with and without the extra chromosome silenced, to reveal the genes and pathways most consistently perturbed by the extra chromosome in Down syndrome, and identify a set of genes markedly affected on other chromosomes. This project will lay the foundation for the potential development of "chromosomal therapy" for prevention or treatment of leukemia and other complications of Down syndrome and should, more immediately, identify potential targets for more conventional drug or gene therapy.