Researchers at the Center for Childhood Cancer Research, including Carolyn A. Felix, MD, are performing preclinical investigations into the use of the well-known antiviral agent ribavirin as a treatment for acute lymphoblastic leukemia (ALL) in infants less than one year old, which is largely MLL-rearranged and has a poor prognosis.

The eukaryotic translation initiation factor eIF4E is a cellular protein that causes export of many mRNAs from the nucleus to the cytoplasm and/or their translation from mRNAs into proteins. In their investigations into a different anticancer drug, researchers at the Center for Childhood Cancer Research discovered that the eIF4E signaling pathway is frequently upregulated in infant ALL.

This discovery was fortuitous because others recently suggested that ribavirin, which previously was safely used for decades as an antiviral drug, inhibits eIF4E and has anti-leukemia activity against adult leukemia without the toxicities of conventional chemotherapies.

The studies in progress at the Center for Childhood Cancer Research are propagating primary infant ALL cells on bone marrow stromal layers as well as in mouse models in order to investigate the extent to which targeting eIF4E with ribavirin can inhibit leukemia cell proliferation and survival in infant ALL. They also are investigating the preclinical activity of ribavirin-chemotherapy combinations.

ALL in infants has poor prognosis both because of the MLL rearrangement and the vulnerability of infants to treatment complications. The goal of this research is to further develop ribavirin and ribavirin combinations into a molecularly targeted strategy with a low toxicity profile to treat infant ALL.