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  • Title: Alteration in the cellular response to retinoic acid of a human acute promyelocytic leukemia cell line, UF-1, carrying a patient-derived mutant PML-RARalpha chimeric gene.
    Author: Sato A, Imaizumi M, Hoshi Y, Rikiishi T, Fujii K, Kizaki M, Kagechika H, Kakizuka A, Hayashi Y, Iinuma K.
    Journal: Leuk Res; 2004 Sep; 28(9):959-67. PubMed ID: 15234573.
    Abstract:
    Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Although the mutant protein showed a decreased ligand-dependent transcriptional activity and retained a dominant-negative effect on normal RARalpha, UF-1 cells underwent growth inhibition, maturation and apoptosis in response to ATRA at 1 microM, but not < or = 100 nM, after 4 days of treatment with ATRA. Moreover, in the presence of 1 microM ATRA, approximately 50% of UF-1 cells expressing annexin V, an early-apoptotic marker, was negative for CD11b and showed immature morphology. These findings suggest that UF-1 cells, despite expressing mutant PML-RARalpha protein, can be induced by ATRA to undergo differentiation and apoptosis through RA-inducible mechanism(s), in which a proportion of apoptosis may occur independent of terminal differentiation. This unique cell line may be useful for investigating the pathogenesis of ATRA resistance and the mechanism of ATRA-induced apoptosis in APL.
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