CRLF2 defects in Down syndrome-associated leukemia

A chromosomal alteration that fuses the P2RY8 and CRLF2 genes is found in individuals with B-progenitor acute lymphoblastic leukemia (ALL) and ALL associated with Down syndrome (DS), according to a new study published online this week in Nature Genetics.

ALL is the most common childhood cancer, with a cure rate of 85% in children. Children with DS are approximately 10-20 times more likely to develop leukemia than non-DS children.

Charles Mullighan and colleagues report that a recurrent chromosomal deletion that leads to the P2RY8-CRLF2 fusion is found in 7% of individuals with B-progenitor ALL and 53% of individuals with Down syndrome-associated ALL. The fusion leads to elevated activity of the CRLF2 gene, which may contribute to the increased risk of ALL in children with DS.