Neplanocin A, a potent inhibitor of S-adenosylhomocysteine hydrolase, potentiates granulocytic differentiation of acute promyelocytic leukemia cells induced by all-trans retinoic acid.
Exp Hematol
; 25(12): 1296-303, 1997 Nov.
Article
en En
| MEDLINE
| ID: mdl-9357974
ABSTRACT
Several neplanocin A analogs were synthesized and their growth-inhibiting and differentiation-inducing activities on myelogenous leukemia cells were examined. An adenosine kinase-ineffective analog of neplanocin A was effective in inducing differentiation, suggesting that phosphorylation of the nucleoside is not essential for inducing the differentiation of leukemia cells. Neplanocin A induced functional and morphological differentiation of HL-60 cells, but did not effectively induce differentiation of NB4, a cell line derived from a leukemia patient with t(15;17). However, these cells have been known to undergo granulocytic differentiation upon treatment with all-trans retinoic acid (ATRA), and are used as a model for differentiation therapy in acute promyelocytic leukemia. Preexposure of NB4 cells to low concentrations of neplanocin A greatly enhanced the ATRA-induced differentiation of the cells, whereas representative antileukemic drugs such as cytosine arabinoside and daunomycin did not enhance this differentiation. A clinical strategy that combines intermittent treatment with neplanocin A analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.
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Bases de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Leucemia Promielocítica Aguda
/
Adenosina
/
Inhibidores Enzimáticos
/
Granulocitos
/
Hidrolasas
/
Antibióticos Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Exp Hematol
Año:
1997
Tipo del documento:
Article
País de afiliación:
Japón