Evidence for negative feedback of extracellular methotrexate on blasts of acute lymphoblastic leukemia in vitro.
Pharmacotherapy
; 17(6): 1260-6, 1997.
Article
en En
| MEDLINE
| ID: mdl-9399609
ABSTRACT
STUDY OBJECTIVE:
To explore the value of high-dose methotrexate (MTX).SUBJECTS:
Blast cells from 15 patients with acute lymphoblastic leukemia.INTERVENTIONS:
We compared uptake and polyglutamation of [3H]-MTX by freshly isolated leukemic blasts in vitro after 24-hour exposure to 1, 10, and 50 microM [3H]-MTX. MEASUREMENTS AND MAINRESULTS:
Mean MTX uptake (pmol/10(6) cells) was 0.78 +/- 0.19, 2.3 +/- 0.54, and 5.9 +/- 1.9, respectively, and mean polyglutamation was 82%, 66%, and 46%. Consequently, mean MTX polyglutamates were 0.68 +/- 0.18, 1.5 +/- 0.47, and 2.2 +/- 0.67 pmol/10(6) cells. Three of 15 patient samples had no detectable polyglutamation of MTX at 50 microM but MTX polyglutamates were detectable at 1 microM. Two of these three had a decrease in MTX polyglutamates at 10 versus 1 microM. In eight precursor B cell samples there was a significant difference in median MTX polyglutamates at 1 versus 10 microM but not 10 versus 50 microM.CONCLUSION:
Increasing extracellular MTX concentrations may be counterproductive for some patients with acute lymphoblastic leukemia. If MTX polyglutamates are important for efficacy, optimal delivery of MTX may have to be determined by individual metabolism rather than by targeting a specific drug concentration.
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Banco de datos:
MEDLINE
Asunto principal:
Metotrexato
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antimetabolitos Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Pharmacotherapy
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos