RESEARCHERS AWARDED NCI GRANT TO STUDY BIOLOGY AND TARGETING OF NONCODING RNAs IN AML

A five-year, $1.95 million grant from the National Cancer Institute (NCI) will help a research team at the OSUCCC – James study how a certain long non-coding RNA (lncRNA) contributes to a common form of cytogenetically normal acute myeloid leukemia (CN-AML) and determine whether blocking the lncRNA is a viable targeted therapy.

Some 45-50% of AML cases are cytogenetically normal, meaning they have no chromosomal abnormalities. However, novel recurrent gene mutations recently have been identified in CN-AML. The most common among those are mutations in the nucleophosmin (NPM1) gene, and researchers at the OSUCCC – James have discovered that abnormally high levels of a lncRNA called HOXB-AS3 in the leukemic cells of patients with NPM1-mutated AML enables the rapid growth and proliferation of malignant blast (immature) cells.

The researchers, led by Ramiro Garzon, MD, a professor in the Division of Hematology at Ohio State and co-leader of the Leukemia Research Program at the OSUCCC – James, also have shown that reducing HOXB-AS3 decreases blast proliferation and cell colony formation in AML cell lines and in patients with primary AML. In addition, they have demonstrated that silencing HOXB-AS3 in mouse models of human disease led to increased survival among those mice.

Those findings were published late last year in the journal Nature Communications.

“Altogether,” the researchers state in the abstract to their new grant-funded project, “our preliminary data supports our hypothesis that HOXB-AS3 plays an important role in NPM1-mutated AML, and that blocking HOXB-AS3 may be a viable therapeutic target in (patients with this disease).”

The overall goal of this project, they add, is “to dissect the mechanisms through which HOXB-AS3 contributes to myeloid leukemogenesis (leukemia origin) and to explore how to target therapeutically this lncRNA.” 

At the completion of this project, the scientists believe they “will have an increased understanding of the role of lncRNAs in NPM1-mutated AML” so that their findings may be incorporated into future treatment strategies that could improve outcomes for patients with this cancer.

Despite advances that have led to better outcomes for some patients with AML in recent years, the researchers note that the overall prognosis for AML is still very poor.

“Thus,” they write, “understanding mechanisms regulating the biology of AML is important for developing effective therapies for this disease.”