Preserving the power of glucocorticoids to fight leukemia

Erik Bonten, Steven Paugh, William Evans

Steroids called glucocorticoids are part of chemotherapy that has transformed treatment of the most common childhood cancer. Today 94% of St. Jude Children’s Research Hospital patients with acute lymphoblastic leukemia (ALL) will become long-term survivors. But those whose cancer cells are resistant to steroids may not fare as well.

St. Jude scientists searched the cancer genomes of ALL patients to find out how some leukemia cells could resist steroids.

In leukemia cells that resisted the drugs, the genes CASP1 and NLRP3 were more active. NLRP3 makes a protein that works like an “on” switch for CASP1. When scientists reduced CASP1 activity, the steroids worked better against leukemia cells. Scientists also found out why extra CASP1 helped cells resist the drugs.

“The search is on to find small molecules that could help reverse glucocorticoid resistance,” said William Evans, PharmD, Pharmaceutical Sciences. “Glucocorticoids are used to treat asthma, rheumatoid arthritis, colitis and other autoimmune disorders, so these results may benefit a wide range of patients.”

The study appeared in the journal Nature Genetics.

May 4, 2015

Read the news release