A gene within a gene contributes to the aggressiveness of acute myeloid leukemia

PUBLIC RELEASE DATE:

21-Apr-2014

Contact: Darrell E. Ward Darrell.Ward@osumc.edu 614-293-3737 Ohio State University Wexner Medical Center

COLUMBUS, Ohio A small gene that is embedded in a larger, well-known gene is the true leukemia-promoting force usually attributed to the larger gene, according to a new study by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

The findings are published in the journal Science Signaling.

The larger host gene is called BAALC (pronounced "Ball C"). The smaller embedded gene is called microRNA-3151 (miR-3151). The study investigated the degree to which each of the genes contributes to the development of acute myeloid leukemia (AML).

"We discovered that the smaller microRNA gene, and not the larger host gene, is the major oncogenic driver of the two molecules in AML," says principal investigator Albert de la Chapelle, MD, PhD, professor of Medicine and the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research.

"When both genes are highly expressed, it means a bad prognosis for patients, but our experiments indicate that it is high expression of miR-3151 that really matters. Overexpression of BAALC alone had only limited cancer-causing activity," he says.

The researchers discovered that miR-3151 promotes the development of leukemia by blocking a gene called TP53. Normally, TP53 is a central "tumor-suppressor" gene that protects against cancer by causing a cell with serious gene damage to self-destruct. "When miR-3151 blocks TP53 in the tumor cells, it enables the cells to survive, divide and grow faster," says co-senior author Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar.

"We also show that miR-3151 promotes growth in malignant melanoma cells in the same way, suggesting that the molecule might play a role in solid-tumor development," says Bloomfield, who is also senior adviser to the OSUCCC James and holds the William Greenville Pace III Endowed Chair in Cancer Research.

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A gene within a gene contributes to the aggressiveness of acute myeloid leukemia