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Study finds tumor suppressor may actually fuel aggressive leukemia
Date:8/27/2013

CINCINNATI New research in the Journal of Clinical Investigation suggests that blocking a protein normally credited with suppressing leukemia may be a promising therapeutic strategy for an aggressive form of the disease called acute myeloid leukemia (AML).

Researchers from Cincinnati Children's Hospital Medical Center report their results in a study posted online Aug. 27 by the journal.

The protein scientists targeted is a transcription factor known as RUNX1, which also plays an important role in helping regulate the normal development of blood cells. The researchers were surprised to discover in their laboratory tests that RUNX1 was supporting the growth of AML fueled by what are called fusion proteins.

"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 in patients, 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. Researchers like Mulloy are searching for improved treatment strategies, including targeted molecular approaches that could potentially be more effective and carry fewer side effects.

They tested this finding in a genetic mouse model of AML developed by Mulloy's laboratory that is driven by fusion proteins and a mixed-lineage leukemic gene called MLL-AF9. The researchers genetically inhibited both RUNX1 and an associated protein called core-binding factor subunit beta (Cbfb). By doing so, the researchers were able to stop the development of leukemia cells, demonstrating the potent
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Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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