A retinoid acid 'resistant' t (15;17) acute promyelocytic leukemia cell line: isolation, morphological, immunological, and molecular features
Duprez, E.; Ruchaud, S.; Houge, G.; Martin-Thouvenin, V.; Valensi, F.; Kastner, P.; Berger, R.; Lanotte, M.
Leukemia 6(12): 1281-1287
1992
ISSN/ISBN: 0887-6924 PMID: 1453773 Document Number: 393803
We report the isolation of a maturation-resistant acute promyelocytic leukemia (APL) cell line. This permanent cell line, derived from the same patient as the maturation inducible NB4 cell line, is the first retinoid-resistant cell line with a t(15;17) chromosomal translocation. Morphological, immunocytochemical and molecular features of the maturation responsive (NB4) and unresponsive (NB4-RA') cells are compared. The isolation of the NB4-RA' cell line occurred through a two-step process requiring the continuous selective pressure of all-trans-retinoic acid. Cells are also resistant to 13-cis-retinoic acid. Karyotypic and Southern-blot analyses show that the two cell lines are similar with respect to the translocation. Northern-blot analyses show that the chimeric fusion transcript PML-RAR-alpha and the normal allelic PML and RAR-alpha transcripts are similarly expressed in both cell lines. The molecular basis for unresponsiveness to retinoic acid is not known. This resistant cell line offers a cellular model for molecular biology studies on the mechanism of induction of APL cell maturation, as well as a means to elucidate the molecular mechanisms of resistance. It also furnishes a unique tool for designing and/or screening new therapeutic drugs to avoid or relieve retinoid maturation blockage.