Methylthioadenosine phosphorylase (MTAP)-deficient T-cell ALL xenografts are sensitive to pralatrexate and 6-thioguanine alone and in combination.
Cancer Chemother Pharmacol
; 75(6): 1247-52, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-25917288
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tioguanina
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Purina-Nucleósido Fosforilasa
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Xenoinjertos
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Aminopterina
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Antineoplásicos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Alemania