Juvenile myelomonocytic leukemia (JMML) is a blood cancer that affects young children and is often difficult to diagnose and treat. Currently available therapies cure only half of patients, with some children experiencing an aggressive disease course while a rare group get better with very little treatment. We have now shown that presence of secondary mutations at diagnosis predicts a poor outcome. We have also shown that DNA methylation profiling can identify patients most likely to experience favorable outcomes.
We are currently running a clinical trial through the Children's Oncology Group for patients with relapsed and refractory JMML. This trial is testing the safety and efficacy of the oral MEK inhibitor, trametinib. This trial is based on extensive pre-clinical testing and a strong genomic rationale. This trial marks an important step towards more effectively treating patients with Ras driven leukemia using targeted agents.
Our next trial will risk-stratify patients with newly diagnosed JMML to receive different therapies tailored to the risk of relapse predicted by both the number of mutations and DNA methylation signatures at diagnosis.