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【文摘发布】《Blood》新 RUNX1 亚型通过控制 CD5
CD56high acute myeloid leukemias (AMLs) have a poor prognosis, but it has been unclear how CD56 expression is controlled and how it relates to clinical aggressiveness. We show that CD56 expression on AML cells correlates with an abnormal expression pattern of runt-related transcription factor 1 (RUNX1) isoforms. Whereas full-length p48 RUNX1 (p48) up-regulated CD56 in AML cells, 3 previously unknown shorter RUNX1 isoforms, p38a, p30, and p24, suppressed CD56 expression. Both p48 and CD56 induced nuclear translocation of nuclear factor (NF)–B and increased bcl2L12 expression, and inhibition of this pathway by small inhibitory RNA-mediated p48 knock down or NF-B blockade substantially increased apoptosis in CD56+ AML cell lines. These findings indicate the potential for new therapy of CD56high AML by suppression of the "overactive" RUNX1/CD56/NF-B signaling pathway.
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/110/6/2027 Novel RUNX1 isoforms determine the fate of acute myeloid leukemia cells by controlling CD56 expression
新RUNX1亚型通过控制CD56表达决定AML细胞的命运运
CD56high acute myeloid leukemias (AMLs) have a poor prognosis, but it has been unclear how CD56 expression is controlled and how it relates to clinical aggressiveness.
CD56高表达的AMLs预后差，但是还不清楚CD56表达是如何调控的，以及它为什么与临床侵袭性相关。
We show that CD56 expression on AML cells correlates with an abnormal expression pattern of runt-related transcription factor 1 (RUNX1) isoforms. Whereas full-length p48 RUNX1 (p48) up-regulated CD56 in AML cells, 3 previously unknown shorter RUNX1 isoforms, p38a, p30, and p24, suppressed CD56 expression.
我们发现AML细胞的CD56表达与RUNX1亚型的异常表达模式相关。而在AML细胞中，全长p48RUNX1上调CD56，3个先前未知的短RUNX1亚型，p38a, p30和 p24抑制CE56表达。
Both p48 and CD56 induced nuclear translocation of nuclear factor (NF)–B and increased bcl2L12 expression, and inhibition of this pathway by small inhibitory RNA-mediated p48 knock down or NF-B blockade substantially increased apoptosis in CD56+ AML cell lines.
p48和CD56均能诱导NF–B核转位，通过小抑制RNA介导的p48敲除或NF-B阻滞来抑制此通路，增加了AML细胞株凋亡。
These findings indicate the potential for new therapy of CD56high AML by suppression of the "overactive" RUNX1/CD56/NF-B signaling pathway
这些发现表明，抑制过度活化的RUNX1/CD56/NF-B CD56信号通路也许可能成为CD56高表达AML患者的新的治疗方法。
新RUNX1亚型通过控制CD56表达决定AML细胞的命运运
CD56高表达的AMLs预后差，但是还不清楚CD56表达是如何调控的，以及它如何与临床侵袭性相联系的。我们发现AML细胞CD56表达与RUNX1亚型的异常表达模式相关。而在AML细胞中，全长p48RUNX1上调CD56，3个先前未知的短RUNX1亚型，p38a, p30和 p24抑制CD56表达。p48和CD56均能诱导NF–B核转位，通过SiRNA介导的p48敲除或NF-B阻滞来抑制此通路，增加了AML细胞株凋亡。这些发现表明，抑制过度活化的RUNX1/CD56/NF-B CD56信号通路也许可能成为CD56高表达AML患者的新的治疗方法。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-01-24 05:34
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