JNCI paper details subunits of SWI/SNF complex linked to glucocorticoid resistance.
Researchers at the Institut National de la Sante’ et de la Recherche Medicale have discovered that expression of components of the SWI/SNF chromatin-remodeling complex is associated with resistance to glucocorticoids, which are components of therapy for childhood acute lymphoblastic leukemia (ALL).
“To our knowledge for the first time, we found an association between the expression of as many as three genes encoding key subunits of the SWI/SNF complex—SMARCA4, SMARCB1, and ARID1A—and resistance of ALL cells to prednisolone,” the authors write in their paper, which appears in the December 9 Journal of the National Cancer Institute.
The team examined the expression of genes encoding the SWI/SNF complex in ALL cells isolated from pediatric patients. The researchers compared gene expression with sensitivity to prednisolone and dexamethasone in independent training and validation cohorts.
Expression of three SWI/SNF genes was associated with resistance to the two drugs and expression of a fourth gene was associated with prednisolone resistance. Reducing the expression of SMARCA4 in a glucocorticoid-sensitive ALL cell line increased this cell line’s resistance to prednisolone.