Targeting the RUNX1
protein – a transcription factor that helps regulate blood cell development –
may provide a new approach to treating acute myeloid leukemia (AML), according
to a study led by researchers at Cincinnati Children’s.
The findings, posted online Aug. 27, 2013, in
the Journal of Clinical Investigation, found
that RUNX1 plays an unexpected role
in supporting the growth of AML when the condition is fueled by fusion
“RUNX1 is generally
considered a tumor suppressor in myeloid neoplasms, but our study found that
inhibiting its activity rather than enhancing it could be a promising
therapeutic strategy for AMLs driven by fusion proteins,” said James Mulloy PhD, a researcher in the Division of Experimental Hematology and Cancer Biology
at Cincinnati Children’s and lead investigator.
AML develops and
progresses rapidly, requiring prompt treatment with chemotherapy, radiation or
bone marrow transplant. These treatments can be risky or only partially
effective depending on the patient as well as the variation and progression of
disease. Mulloy and colleagues are searching for targeted molecular approaches
that could be more effective and carry fewer side effects.
The research team
developed a mouse model of AML that is driven by fusion proteins and a mixed-lineage
leukemic gene called MLL-AF9. When researchers genetically inhibited RUNX1 and an
associated protein called core-binding factor subunit beta (Cbfb) in these
mice, it stopped the development of leukemia cells.
based on mouse models do not always translate to human disease, the findings demonstrate
that RUNX1 merits further research as a potential therapeutic target for AML.