Enzyme inhibitor could counter bad ‘seeds’ that let leukemia bounce back

Enzyme inhibitor could counter bad ‘seeds’ that let leukemia bounce back

Leukemia is notorious for being very aggressive and hard to eradicate from the body. The culprits are leukemic stem cells—known as “seed” cells—that drive resistance to chemotherapy and can trigger a relapse of the cancer.

Now, a team led by William Grey, Ph.D, of the Haematopoietic Stem Cell Laboratory at London’s Francis Crick Institute, has discovered a small molecule inhibitor that may hold the key to suppressing these seed cells.

Inhibiting an enzyme called CKS1 shrank cultured leukemic stem cells derived from patients, the researchers noted in their study published June 22 in the journal Science Translational Medicine. What’s more, when the same CKS1 inhibitor was grafted onto mice, it had the added bonus of protecting their normal cells from the toxic effects of the chemotherapy drugs doxorubicin and cytarabine.

The mice with acute myeloid leukemia (AML) that received these two drugs along with the inhibitor showed longer survival times and higher amounts of healthy stem cells compared with those that received the chemotherapy alone, the researchers noted. They attributed this to the drug’s ability to accelerate the production of highly reactive chemicals called cell-killing reactive oxygen species in the seed cells.

The researchers suggested that a similar regimen of CKS1 inhibitor therapy could reduce leukemia relapse rates and improve treatment outcomes in human patients with the disease. As it stands, patients with AML often relapse after suffering severe side effects from their chemotherapy, resulting in an average survival time of just two years, they said.

“The selective reduction of leukemic cells by CKS1 inhibition demonstrates that precisely targeting proteostatic regulators can be a new avenue in AML therapy,” the researchers said.

The study focused on poor-risk patients with AML and further work is needed to evaluate the role of these inhibitors on intermediate- and good-risk AML patient groups, they added.

But the benefits may not end with leukemia. Some types of solid tumors have also been linked to over-expression of the CKS1B gene, which opens up the possibility that these inhibitors could one day be applied to a broader range of cancers.

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