New Drug Shows Potential in Treatment of Rare Leukemia

Drug could eventually also treat prostate cancer.

A new compound exhibited potential in the treatment of a rare form of leukemia, a recent study indicates.

The drug was developed following several years of research on a small-molecule inhibitor that blocks the interaction between the protein menin and MLL fusion proteins, which cause a rare type of acute leukemia. MLL fusion leukemia comprises nearly 10% of acute leukemia in adults, and approximately 70% of the disease in infants, the study noted.

As a result of ineffective current therapies, just over one-third of patients survive 5 years. The menin-MLL fusion protein interactions represents a significant challenge in the development of drugs that target these interactions.

"In many types of cancer, you see multiple interactions and mutations that trigger the cancer,” co-study lead Jolanta Grembecka, PhD, said in a press release. “The MLL-menin interaction is a good drug target because it's the primary driver in this type of leukemia. By blocking this interaction, it's very likely to stop the cancer.”

For the study, recently published in Cancer Cell, investigators evaluated a pair of compounds, called MI-463 and MI-503, in cell lines and mice with MLL leukemia. The results showed the compounds blocked MLL-menin interaction without affecting normal blood cells.

The compounds entered the blood and metabolized at a solid rate, the study noted, which are both vital to the development of new drugs.

During the current study, researchers were able to substantially enhance the potency of the compound and improved pharmacologic properties, which makes it more feasible for use in humans.

"Against all odds, we decided to explore finding a way to block the MLL-menin interaction with small molecules,” co-study lead Tomasz Cierpicki, PhD, said in a press release. “From nothing, we have been able to identify and greatly improve a compound and show that it's got valuable potential in blocking MLL fusion leukemia in animal models.”

In another evaluation, prostate cancer researchers found that menin and MLL play a role in androgen receptor signaling. A study published recently in Nature Medicine evaluated MI-463 and MI-503 for the treatment of castration resistant prostate cancer cells and mouse models.

"Our study suggests that this MLL-menin inhibitor might also have a potential role in a more common solid tumor, in this case prostate cancer," senior author Arul M. Chinnaiyan, MD, PhD, said in a press release.