| First Author | Nguyen TB | Year | 2020 |
| Journal | Cancer Res | Volume | 80 |
| Issue | 9 | Pages | 1875-1884 |
| PubMed ID | 32107212 | Mgi Jnum | J:288535 |
| Mgi Id | MGI:6416190 | Doi | 10.1158/0008-5472.CAN-19-2787 |
| Citation | Nguyen TB, et al. (2020) Dasatinib Is an Effective Treatment for Angioimmunoblastic T-cell Lymphoma. Cancer Res 80(9):1875-1884 |
| abstractText | Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulated T-cell receptor (TCR) signaling. Using these mice to investigate therapeutics for AITL, we found that dasatinib, a multikinase inhibitor prolonged their survival through inhibition of hyperactivated TCR signaling. A phase I clinical trial study of dasatinib monotherapy in 5 patients with relapsed/refractory AITL was performed. Dasatinib was started at a dose of 100 mg/body once a day and continued until days 10-78 (median day 58). All the evaluable patients achieved partial responses. Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment. SIGNIFICANCE: Deregulated T-cell receptor signaling is a critical molecular event in angioimmunoblastic T-cell lymphoma and can be targeted with dasatinib. |
