All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Chomienne C,Ballerini P,Balitrand N,Daniel MT,Fenaux P,Castaigne S,Degos L

subject

Has Abstract

pub_date

1990-11-01 00:00:00

pages

1710-7

issue

9

eissn

0006-4971

issn

1528-0020

journal_volume

76

pub_type

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