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[【学科前沿】] 通过维持法可以诱导急性淋巴白血病的分化

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eye2009 该用户已被删除
发表于 2008-4-15 10:33:55 | 显示全部楼层 |阅读模式
Induction of acute lymphocytic leukemia differentiation by maintenance therapy
Despite extensive study in many malignancies, maintenance therapy has clinically benefited only two diseases: acute lymphocytic leukemia (ALL) and acute promyelocytic leukemia (APL).
尽管广泛的研究了多种恶性肿瘤,但维持疗法在临床上仅仅用于两种疾病:急性淋巴白血病(ALL)和急性骨髓性白血病(APL)。

ALL maintenance therapy utilizes low-dose 6-mercaptopurine (6MP) and methotrexate (MTX), while maintenance in APL primarily consists of all-trans-retinoic acid (ATRA).
所有的维持疗法都使用低剂量的6-巯基嘌呤(6MP)和甲氨蝶呤(MTX),在APL初期的维持治疗中还要联合使用全反式维甲酸(ATRA)。

6MP and MTX as used in ALL are also now usually added to maintenance ATRA for APL, based on data suggesting an improved disease-free survival.
所有的维持疗法在习惯上都使用6MP和MTX,根据加强无病生存的建议,现在APL的治疗中增加了ATRA。

Although the mechanism of action of MTX and 6MP as maintenance is unknown, low-dose cytotoxic agents are potent inducers of differentiation in vitro.
虽然MTX和6MP作为维持治疗的作用机制还不知道,但体外的低剂量细胞毒实验显示他们是有效的分化诱导物。

Thus, we studied whether maintenance therapy in ALL, like ATRA in APL, may be inducing terminal differentiation of ALL progenitors.
像在APL上使用ATRA一样,我们研究的所有维持疗法都可以诱导原生组织分化。

The APL cell line NB4, the ALL cell lines REH and RS4;11, and patients' ALL blasts were incubated with ATRA, 6MP, and MTX in vitro.
APL的细胞株NB4,ALL的REH和RS:11细胞株,以及ALL患者的瘤体都用ATRA、6MP和MTX做体外培养。

All three drugs inhibited the clonogenic growth of the APL and ALL cell lines without inducing immediate apoptosis, but associated with induction of phenotypic differentiation.
单独使用三种药都要抑制 APL和ALL细胞株的生长但不会直接导致细胞死亡,而联合使用可以引起表型分化。

The three drugs similarly upregulated lymphoid antigen expression, while decreasing CD34 expression, on patients' ALL blasts.
三种药同样调节淋巴抗原的表达,当减少白细胞分化抗原抗体(CD34)的表达时,患者的ALL就完蛋了。

These data suggest that induction of leukemia progenitor differentiation plays an important role in the mechanism of action of maintenance therapy in ALL.
这些资料表明,在ALL的维持治疗中白血病祖细胞的分化扮演着一个重要的角色
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