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Effect of Tissue Transglutaminase on Steroid Resistance in T-Cell Acute Lymphoblastic Leukemia

초록/요약

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.

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목차

I 서론 (Introduction) 1
II 본론 3
A. 실험방법 (Materials and Methods) 3
1. Cell lines and cell maintenance 3
2. Reagents 3
3. Immunofluorescence analysis 4
4. Immunoblot analysis 4
5. Tissue transglutaminase (TG2) enzymatic activity assay 5
6. Colorimetric cell viability assay 5
7. Flow cytometry 5
8. Nuclear factor-κB (NF-κB) activity assay 6
9. Statistical analysis 6
B. 실험결과 (Results) 7
1. TG2 expression in T-cell acute lymphoblastic leukemia (T-ALL) cells. 7
2. Generation of steroid-adapted (SA) T-ALL cells 9
3. Steroid adaptation affects TG2 and NF-κB activity in T-ALL. 12
4. TG2 inhibition reduces steroid resistance in SA T-ALL. 14
III 결론 (Discussion) 19
참고문헌 23

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