Effect of tissue transglutaminase on steroid resistance in T-cell acute lymphoblastic leukemia

Abstract

Aim: To improve survival in patients with glucocorticoid-resistant T-cell acute lymphoblastic leukemia (T-ALL), it is critical to develop new therapeutic strategies to overcome steroid resistance. Materials and Methods: Biochemical and molecular methodologies were used to evaluate whether tissue transglutaminase (TG2) confers steroid resistance in T-ALL. Results: T-ALL cells were found to express elevated levels of TG2. Models of steroid-adapted subclones of T-ALL cell lines which were notably less sensitive to steroids than the parental cells. The steroid-adapted subclones showed increased TG2 expression and nuclear factor-ĸB (NF-ĸB) activity compared to T-ALL parental cells. Inhibition of TG2 suppressed steroid resistance and improved steroid cytotoxicity in steroid-adapted subclones of T-ALL in association with reduced NF-ĸB activity. Conclusion: TG2 may serve as a new target to overcome steroid resistance in T-ALL.