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. We went on to generate models of steroid-adaptedsubclonesofT-ALLcelllinesthatwerenotablylesssensitivetosteroidsthantheparental cells. The steroid-adapted subclones showed increased TG2 expression and nuclear factor-κB (NF-κB) 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-κB activity. CONCLUSION: It is important to note that this study identified that possible changes in TG2 expression may serve as a new target aimed at overcoming steroid resistance in T-ALL.