Credit: Aaron Logan
Researchers say they’ve uncovered a genetic defect in acute lymphoblastic leukemia (ALL) cells that promotes their invasion of the brain.
The team believes the findings, recently published in Genes & Development, could lead to the development of therapies that specifically prevent ALL spread to the central nervous system (CNS).
Currently, curing children with ALL often requires injections of chemotherapy directly into the CNS to limit leukemia growth.
But these therapies can cause long-term health issues.
“If we can find therapies to prevent leukemia spread to the brain, instead of injecting chemotherapy into the brain, that would be huge,” said study author Cynthia Guidos, PhD, of The Hospital for Sick Children (SickKids) in Toronto, Canada.
“Our findings suggest that drugs targeting the functions controlled by a gene called Flt3 could help block leukemic cell growth in the CNS and may be less toxic than current treatments.”
Using a mouse model, the researchers found that CNS-invading leukemias expressed higher levels of Flt3 than leukemias that did not spread to the CNS.
And the CNS-invading leukemias expressed a defective version of Flt3 that cannot be turned off, suggesting that Flt3 allows the leukemic cells to invade the CNS.
The researchers transferred the defective Flt3 gene into mouse leukemia cells that don’t usually invade the brain. And this endowed them with the ability to spread to the CNS.
The team also showed that a Flt3 inhibitor halted growth of the CNS leukemia cells in vitro.
Dr Guidos said the next step for this research will be to investigate whether Flt3 also plays an important role in promoting CNS invasion of human ALL.
She and her colleagues plan to use frozen cells from the SickKids leukemia cell bank, which contains frozen samples from more than 100 patients, to do just that.
