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- Title
Methylthioadenosine phosphorylase (MTAP)-deficient T-cell ALL xenografts are sensitive to pralatrexate and 6-thioguanine alone and in combination.
- Authors
Tedeschi, Philip; Kathari, Yamini; Johnson-Farley, Nadine; Bertino, Joseph
- Abstract
Purpose: To investigate the effectiveness of a combination of 6-thioguanine (6-TG) and pralatrexate (PDX) in methylthioadenosine phosphorylase (MTAP)-deficient T-cell acute lymphoblastic leukemia (T-cell ALL). Methods: CCRF-CEM (MTAP) and Molt4 (MTAP) T-cell ALL cell lines were treated with 6-TG or PDX and evaluated for efficacy 72 h later. NOD/SCID gamma mice bearing CEM or Molt4 xenografts were treated with 6-TG and PDX alone or in combination to evaluate antitumor effects. Results: CEM cells were more sensitive to 6-TG and PDX in vitro than Molt4. In vivo, CEM cells were very sensitive to PDX and 6-TG, whereas Molt4 cells were highly resistant to 6-TG. A well-tolerated combination of PDX and 6-TG achieved significant tumor regression in CEM xenografts. Conclusions: The loss of MTAP expression may be therapeutically exploited in T-cell ALL. The combination of 6-TG and PDX, with the inclusion of leucovorin rescue, allows for a safe and effective regimen in MTAP-deficient T-cell ALL.
- Subjects
LYMPHOBLASTIC leukemia treatment; METHYLTHIOADENOSINE; PHOSPHORYLASES; T cells; PTERIDINES; XENOGRAFTS; PURINES
- Publication
Cancer Chemotherapy & Pharmacology, 2015, Vol 75, Issue 6, p1247
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-015-2747-2