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全反式维甲酸与粒细胞集落刺激因子联合诱导维甲酸耐药急性早幼粒细胞白血病细胞分化

Induction of differentiation of retinoic acid-resistant acute promyelocytic leukemia cells by the combination of all-trans retinoic acid and granulocyte colony-stimulating factor.

作者信息

Higuchi Takakazu, Kizaki Masahiro, Omine Mitsuhiro

机构信息

Division of Hematology, Internal Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227-8501, Japan.

出版信息

Leuk Res. 2004 May;28(5):525-32. doi: 10.1016/j.leukres.2003.09.014.

DOI:10.1016/j.leukres.2003.09.014
PMID:15068906
Abstract

An acute promyelocytic leukemia (APL) cell line with natural resistance to all-trans retinoic acid (ATRA), UF-1, was induced to differentiate into mature granulocyte when treated with the combination of ATRA and granulocyte colony-stimulating factor (G-CSF), while neither of them alone was capable of inducing the differentiation effectively. Continuous presence of both agents was required for the maximal differentiation-inductive effect. Neither proliferation arrest nor induction of apoptosis preceded the differentiation. Differentiated phenotype was accompanied by growth arrest, however, not by increased apoptosis. It was assumed that cellular events at the downstream of the signaling pathways of ATRA and G-CSF cooperatively played pivotal roles in the differentiation-induction.

摘要

一种对全反式维甲酸(ATRA)具有天然抗性的急性早幼粒细胞白血病(APL)细胞系UF-1,在用ATRA和粒细胞集落刺激因子(G-CSF)联合处理时,可诱导分化为成熟粒细胞,而单独使用这两种药物均不能有效诱导分化。为达到最大的诱导分化效果,两种药物需持续存在。在分化之前既没有增殖停滞也没有凋亡诱导。分化表型伴随着生长停滞,但凋亡没有增加。据推测,ATRA和G-CSF信号通路下游的细胞事件在诱导分化中共同发挥关键作用。

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