Robert Autry (left), of St. Jude and a graduate student at the University of Tennessee Health Science Center; and William Evans, Pharm.D., of the St. Jude Department of Pharmaceutical Sciences.
Resistance to steroids is a common reason why leukemia treatment fails. What causes resistance is often unknown.
St. Jude Children’s Research Hospital scientists developed a way to discover the genes responsible. The findings could help children and adults with acute lymphoblastic leukemia (ALL).
The scientists used three methods to find genes most strongly linked to steroid resistance. Then they used state-of-the-art tools like CRISPR gene editing to spot which genes to prioritize.
The method revealed 14 new genes linked to steroid resistance. The strongest evidence was against a gene called CELSR2. This gene was expressed at a low level in almost half of patients whose ALL was drug resistant.
Researchers figured out how the gene helped leukemia cells survive steroid treatment. They also found another drug that helps make steroids effective again.
“The finding points to the possible benefit of adding the drug to current therapy as a way to overcome steroid resistance,” said William Evans, PharmD, of the Department of Pharmaceutical Sciences.
This work appeared in the journal Nature Cancer.
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