In healthy bodies, our cells grow and divide in a very controlled way. But when something goes wrong, cells may start dividing too quickly and growing in places they shouldn’t. This uncontrolled growth leads to cancer.

One reason cancer can occur is when certain important genes stop working properly. Some of these genes are known as tumor suppressor genes. They act like brakes, slowing down cell growth, fixing damaged DNA, or helping faulty cells self-destruct. When tumor suppressor genes are missing or not working, those brakes fail—and cancer can develop.

A gene called CIC (capicua) has been suspected to be one of these tumor suppressors. But until recently, scientists didn’t have a good way to study CIC’s role in cancer in living animals.

Two recent studies helped solve this by creating special genetically engineered mice where CIC could be removed once the mice became adults. This was important because removing CIC earlier in life caused severe health issues.

Once CIC was removed from the adult mice, the researchers saw something striking: the mice died much younger than normal mice. When they looked closer, they found that the mice had enlarged thymi—the organ where a type of immune cell called T cells mature. This symptom pointed to a specific kind of blood cancer called T-cell acute lymphoblastic leukemia (T-ALL).

In T-ALL, T cells don’t mature properly and instead get stuck in an immature state. These immature cells build up in the thymus, causing it to swell and eventually leading to cancer. In one of the studies (the Tan paper), the researchers confirmed this by examining the T cells in the thymus and found a buildup of immature cells and fewer early-stage precursors, showing that the maturation process had stalled.

Both research teams then looked at why CIC loss was leading to cancer.

The Carrasco paper focused on a gene called ETV4, which CIC normally keeps in check. Without CIC, ETV4 levels rose sharply. When the scientists removed both CIC and ETV4 in the mice, tumor growth was almost completely stopped—in 4 out of 5 mice, no signs of cancer appeared even a year later. This suggests that ETV4 plays a major role in causing cancer when CIC is missing.

The Tan paper looked at another gene called MYC, which is a well-known oncogene—a gene that can drive cancer if it becomes overactive. They found that removing CIC caused MYC levels to go up, and this may help explain how the cancer forms in CIC-deficient mice.

In summary, both studies show that CIC is a key tumor suppressor, especially in preventing T-cell leukemia (T-ALL). Losing CIC disrupts the balance of other genes like ETV4 and MYC, which then leads to cancer. These studies not only show how T-ALL develops but also offer mouse models to help scientists test future treatments.

Understanding how CIC works gives researchers new ideas about how to target genes like ETV4 or MYC to stop leukemia from forming—possibly leading to better therapies for T-ALL in the future.

References:

Tan, Q. et al. Loss of Capicua alters early T cell development and predisposes mice to T cell lymphoblastic leukemia/lymphoma. Proc Natl Acad Sci U S A 115, E1511-E1519 (2018). Link to the full text article.

Simon-Carrasco, L. et al. Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma. Genes Dev 31, 1456-1468 (2017). Link to the full text article.