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One Gene Could Be Responsible for Acute Myeloid Leukemia

Laura Joszt

The EVI1 gene may be single-handedly at fault for acute myeloid leukemia (AML), according to research published in Nature Communications. Researchers from the Wilmot Cancer Institute at the University of Rochester Medical Center studied EVI1 in the hopes that a new therapy could improve survival rates for patients with AML.

The researchers were able to show, using a mouse model, how EVI1 binds to certain DNA molecules and disrupts the blood system, leading to the expansion of myeloid cells.

“It’s not so pie-in-the-sky anymore to think we can interrupt the process within the genome that leads to leukemia,” senior author Archibald Perkins, MD, PhD, professor of Pathology and Laboratory Medicine at the University of Rochester Medical Center, said in a statement.

When EVI1 is overexpressed, it changes the metabolism of immature blood cells, and the researchers sought to understand what happens after the gene is overexpressed and permanently turned on. When EVI1 is overexpressed, it produces 10,000 to 50,000 copies. The authors noted that “overexpression of EVI1 is virtually never seen in non-myeloid leukemias or lymphomas.”

Using the mouse model, the researchers showed that skewing toward myeloid production is “dependent on DNA binding by EVI1.”

A targeted therapy that blocks EVI1’s ability to bind to other genes could provide a new approach for treating AML. Currently, the 5-year survival rate for AML is just 25%, despite the fact that treatments for other blood cancers have improved. Overexpression of EVI1 is associated with a median overall survival in AML of just 12 months.

“In summary, our findings offer an insight into mechanisms of leukemogenesis, whereby a single nuclear oncoprotein can induce clinically significant suppression of erythropoiesis and lymphopoiesis, while promoting a shift in differentiation that results in a preleukemic expansion of myeloid cells,” the authors concluded. “These findings help to explain the singular association between EVI1 and myeloid malignancies.”
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