New treatment options for a fatal leukemia

Potential new treatment options for a rare, fatal form of childhood leukemia, for which a long-term cure has never been achieved, are reported in a paper published this week in Nature Genetics. The study also identified specific genetic mutations associated with this form of leukemia.

This particular subset of pediatric acute lymphoblastic leukemia (ALL), a subtype called TCF-HLF positive, accounts for less than 1% of childhood ALL cases, but has a very high rate of disease relapse and death within the first two years after diagnosis.

Jean-Pierre Bourquin, Martin Stanulla and colleagues compared the mutations present in TCF3-HLF positive patients with those of patients with a similar ALL subtype that is responsive to treatment. They identified mutant genes that were specific to the TCF-HLF subtype that may help explain why it is so deadly. With further studies, these mutations could be used as new drug targets. The authors then explored new potential treatment options with existing drugs by transplanting TCF-HLF positive tumor cells from patients into mice and testing them with multiple chemotherapeutic drugs. As expected, standard ALL treatments were not effective, but other classes of drugs showed more promise, including some still in clinical development. One drug, venetoclax, has already shown some efficacy in other ALL subtypes and was particularly effective against TCF3-HLF ALL in mice. The authors suggest venetoclax should be explored as a potential treatment option in these patients.