Comparison of the effects of all-trans and cis-retinoic acid on the blast stem cells of acute myeloblastic leukemia in culture.
Recent work has shown that acute promyelocytic leukemia (APL) cells have a characteristic translocation involving the retinoic acid receptor on chromosome 17 and the myl protein on chromosome 15. Patients with APL respond to the administration of all-trans-retinoic acid. A cell line with t15;17 (NB4) has recently been reported; this line responds to all-trans-retinoic acid with differentiation. There is also a recent report showing that all-trans-retinoic acid is more active than cis-retinoic acid in inducing differentiation in freshly obtained APL cells. All-trans-retinoic and cis-retinoic acid are compared for their effects on growth in culture of freshly obtained AML cells, cell lines without t15;17, and NB4 cells. While all of these AML populations responded to both forms of retinoic acid, NB4 cells only were much more sensitive to all-trans-retinoic acid compared to cis-retinoic acid. The difference was seen when the NB4 cells were exposed in suspension and not when colony-formation in methylcellulose was used as an end point. Both forms of retinoic acid increased the sensitivity of blast cells to cytosine arabinoside; for NB4 cells, the sensitization was much greater when all-trans-retinoic acid was used rather than cis-retinoic acid. We conclude that the increased effects of all-trans-retinoic acid are specific for APL cells, and that a major effect of retinoic acid is on blast stem cell self-renewal.
Tohda
S
S
Ontario Cancer Institute, University of Toronto, Canada.
Curtis
J E
JE
McCulloch
E A
EA
Minden
M D
MD
D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000633:toxicity; D004334:Drug Administration Schedule; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D013237:Stereoisomerism; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003561:Cytarabine; D014212:Tretinoin