Fetal and neonatal hematopoietic progenitors are functionally and transcriptionally resistant to Flt3-ITD mutations

Leukemias are a group of blood cancers that usually arise when immature blood cells gain one or more tumor-promoting genetic mutations. However, for reasons that are not clear, the mutations that cause leukemia are different in children and adults. For example, a mutation called FLT3ITD occurs relatively often in adult leukemia but is rare in infant leukemia. This raises the question of whether the blood cells of fetuses and babies are somehow protected from the effects of the mutation. Porter et al. have now compared the effects of the FLT3ITDmutation in blood cells from adult and fetal mice. In adult mice, the FLT3ITD mutation caused immature blood cells to turn different genes on and off. By contrast, the mutation had no effect on the activity of these genes in fetal mice. Furthermore, only the adult mutant cells showed changes that indicated the early stages of leukemia: the mutant blood cells of fetuses developed as normal. Porter et al. therefore concluded that the immature blood cells of fetuses are protected from the FLT3ITDmutation. To understand why fetal and adult blood cells respond differently to the FLT3ITDmutation, further experiments are needed to investigate how various genes regulate normal blood cell development. In addition, understanding why adult blood cells react to the FLT3ITDmutation might, in the future, lead to better treatment options for leukemia.