Network Toronto, Ontario
Modeling the Initiation and Progression of Down Syndrome Associated Leukemia using CRISPR/Cas9 at Single Cell Resolution
Leukemia is the most common cancer in children, accounting for almost 1 out of 3 cancers. It is even more prevalent in children with Down syndrome, a chromosomal abnormality caused by a third copy of chromosome 21. In particular, children with Down syndrome have a 150-fold increased risk of developing acute myeloid leukemia during the first years of their childhood. In 30% of newborns with Down syndrome a transient pre-leukemia disease occurs. During this pre-leukemia phase, immature white blood cells called megakaryoblasts divide uncontrollably and can cause damage to several tissues, but in most patients it resolves spontaneously. However, in 20% of these cases, the pre-leukemic disease later returns and progresses into full acute myeloid leukemia. The overall aim of the proposal is to understand why an extra copy of chromosome 21 predisposes Down syndrome children to leukemia and to understand the mechanism of leukemia initiation and progression. Dr. Wagenblast’s long-term vision is to prevent the progression of pre-leukemia to acute myeloid leukemia by specifically removing the pre-leukemic cells. This could serve as a general prevention strategy in Down syndrome children diagnosed with pre-leukemia.
Dr. Elvin Wagenblast