Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (32107212)
Authors Nguyen TB, Sakata-Yanagimoto M, Fujisawa M, Nuhat ST, Miyoshi H, Nannya Y, Hashimoto K, Fukumoto K, Bernard OA, Kiyoki Y, Ishitsuka K, Momose H, Sukegawa S, Shinagawa A, Suyama T, Sato Y, Nishikii H, Obara N, Kusakabe M, Yanagimoto S, Ogawa S, Ohshima K, Chiba S
Title Dasatinib Is an Effective Treatment for Angioimmunoblastic T-cell Lymphoma.
Journal Cancer research
Vol 80
Issue 9
Date 2020 05 01
URL
Abstract Text 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.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
ATM D1285G missense unknown ATM D1285G does not lie within any known functional domains of the Atm protein (UniProt.org). D1285G has been identified in sequencing studies (PMID: 32107212), but has not been biochemically characterized and therefore, its effect on Atm protein function is unknown (PubMed, Oct 2020).
TET2 E1207K missense unknown TET2 E1207K lies within the catalytic domain of the Tet2 protein (PMID: 28242787). E1207K has been identified in sequencing studies (PMID: 30279227, PMID: 32107212), but has not been biochemically characterized and therefore, its effect on Tet2 protein function is unknown (PubMed, Oct 2020).
TET2 G1814* nonsense unknown TET2 G1814* results in a premature truncation of the Tet2 protein at amino acid 1814 of 2002 (UniProt.org). G1814* has been identified in sequencing studies (PMID: 32107212), but has not been biochemically characterized and therefore, its effect on Tet2 protein function is unknown (PubMed, Oct 2020).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TET2 T1063Nfs*5 TET2 E1207K angioimmunoblastic T-cell lymphoma predicted - sensitive Dasatinib Case Reports/Case Series Actionable In a clinical case study, four patients with relapsed/refractory angioimmunoblastic T-cell lymphoma harboring TET2 mutations and/or RHOA G17V achieved a partial response within 30 days of Sprycel (dasatinib) treatment, including one patient harboring TET2 T1063Nfs*5 and TET2 E1207K who maintained the partial response past day 60 of treatment (PMID: 32107212). 32107212
TET2 Q958Rfs*49 TET2 R1179Efs*47 angioimmunoblastic T-cell lymphoma predicted - sensitive Dasatinib Case Reports/Case Series Actionable In a clinical case study, four patients with relapsed/refractory angioimmunoblastic T-cell lymphoma harboring TET2 mutations and/or RHOA G17V achieved a partial response within 30 days of Sprycel (dasatinib) treatment, including one patient harboring TET2 Q958Rfs*49 and TET2 R1179Efs*47 who maintained the partial response past day 60 of treatment (PMID: 32107212). 32107212