TY - JOUR
T1 - Occurrence of resistance to retinoic acid in the acute promyelocytic leukemia cell line NB4 is associated with altered expression of the pml/RARα protein
AU - Dermime, S.
AU - Grignani, F.
AU - Clerici, M.
AU - Nervi, C.
AU - Sozzi, G.
AU - Talamo, G. P.
AU - Marchesi, E.
AU - Formelli, F.
AU - Parmiani, G.
AU - Pelicci, P. G.
AU - Gambacorti-Passerini, C.
PY - 1993
Y1 - 1993
N2 - The mechanism(s) by which acute promyelocytic leukemia (APL) cells acquire resistance to all-trans retinoic acid (ATRA) is poorly understood. We describe here an APL cell line, named NB4.306, that shows resistance to the anti-proliferative action of ATRA. This cell line is also operationally resistant to most ATRA-induced phenotypic modifications (CD11b, CD11c, CD13, and CD33). No significant differences in ATRA intracellular accumulation, efflux, or metabolism were found between NB4.306 and the parent NB4 cell line that could explain the observed resistance of the NB4.306 line. The NB4.306 cell line was found to be positive for the t15;17 translocation and showed the usual pml/RARα fusion bands in both Southern and Northern blot assays, but expressed no detectable amount of the usual pml/RARα protein, as assayed by Western blot analysis using an anti-RARα antibody. These results were confirmed in 14 of 14 clones obtained from the NB4.306 cell line, while 30 of 30 clones obtained from the parental NB4 line expressed the usual 110-Kd fusion polypeptide. It is concluded that the occurrence of resistance to ATRA in the NB4.306 cell line is closely associated to the loss of expression of the intact pml/RARα protein.
AB - The mechanism(s) by which acute promyelocytic leukemia (APL) cells acquire resistance to all-trans retinoic acid (ATRA) is poorly understood. We describe here an APL cell line, named NB4.306, that shows resistance to the anti-proliferative action of ATRA. This cell line is also operationally resistant to most ATRA-induced phenotypic modifications (CD11b, CD11c, CD13, and CD33). No significant differences in ATRA intracellular accumulation, efflux, or metabolism were found between NB4.306 and the parent NB4 cell line that could explain the observed resistance of the NB4.306 line. The NB4.306 cell line was found to be positive for the t15;17 translocation and showed the usual pml/RARα fusion bands in both Southern and Northern blot assays, but expressed no detectable amount of the usual pml/RARα protein, as assayed by Western blot analysis using an anti-RARα antibody. These results were confirmed in 14 of 14 clones obtained from the NB4.306 cell line, while 30 of 30 clones obtained from the parental NB4 line expressed the usual 110-Kd fusion polypeptide. It is concluded that the occurrence of resistance to ATRA in the NB4.306 cell line is closely associated to the loss of expression of the intact pml/RARα protein.
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U2 - 10.1182/blood.v82.5.1573.bloodjournal8251573
DO - 10.1182/blood.v82.5.1573.bloodjournal8251573
M3 - Article
C2 - 8395911
AN - SCOPUS:0027258994
VL - 82
SP - 1573
EP - 1577
JO - Blood
JF - Blood
SN - 0006-4971
IS - 5
ER -