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All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro
studies: structure-function relationship
C Chomienne, P Ballerini, N Balitrand, MT Daniel, P Fenaux, S Castaigne and L Degos
Service de Medecine Nucleaire, Hopital Saint Louis, Paris, France.
All-trans retinoic acid induces leukemic cells from patients with acute
promyelocytic leukemia (M3) to differentiate in vitro to mature
granulocytes which express the CD15 antigen and are capable of respiratory
burst function. Of 35 M3 samples, only one failed to respond. In eight
cases, we compared the efficacy of two naturally occurring isomers of
retinoic acid, all-trans RA and 13-cis RA. Both isomers induce maximal
differentiation at 10(-6) mol/L. The maximal response was maintained at
10(-7) mol/L for the all-trans but not for the 13-cis RA. We also observed
that the metabolites 4-oxo-all-trans and 4-oxo-13-cis were effective at
10(-6) mol/L. This 1 order of magnitude difference in the in vitro
differentiating potencies of all- trans RA and 13-cis RA in the blasts of
promyelocytic leukemias predicts a difference in the clinical efficacy of
the two drugs.
Volume 76,
Issue 9,
pp. 1710-1717,
11/01/1990
Copyright © 1990 by The American Society of Hematology
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