PMID: 8609716Dec 1, 1995Paper

In vitro treatment with retinoids or the topoisomerase inhibitor, VP-16, evidences different functional apoptotic pathways in acute promyelocytic leukemic cells

Leukemia
C CalabresseC Chomienne

Abstract

Understanding the mechanisms inherent to malignant cell eradication is a major determinant for cancer therapy. Recent data have demonstrated that apoptosis may be one of the mechanisms through which both cytotoxic and differentiating drugs may eliminate malignant cells. Treatment of acute promyelocytic leukemia (APL) by all-trans retinoic acid (ATRA) is the first model of differentiation therapy allowing achievement of more than 90% complete remission (CR). However, disease-free survival (DFS) is short if patients are not subsequently treated with chemotherapy. In order to address the question of APL cells' elimination during ATRA therapy, we studied phenotypic and molecular features of 14 APL cases relative to cell survival in primary culture in the presence or absence of ATRA. Compared to other acute myeloid leukemia (AML) subtypes, APL cells in short-term suspension culture present a better survival rate (P < 0.001). After incubation with ATRA, cell survival was not altered and was correlated with a concomitant absence of apoptosis, despite a significant decrease of the BcL-2 protein in APL differentiated cells. Indeed, after 6 days of culture, only 3 +/- 0.5% of APL cells exhibit morphological features of apoptosis after AT...Continue Reading

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