Analysis of p73 expression pattern in acute myeloid leukemias:: lack of ΔN-p73 expression is a frequent feature of acute promyelocytic leukemia
Analysis of p73 expression pattern in acute myeloid leukemias:: lack of ΔN-p73 expression is a frequent feature of acute promyelocytic leukemia
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DOI：
10.1038/sj.leu.2403483
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发表时间：
2004-11-01
期刊：
影响因子：
11.4
通讯作者：
Blandino, G
中科院分区：
文献类型：
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作者：
Rizzo, MG;Giombini, E;Blandino, G
p73是p53的同源物，是一种核蛋白，其在p53+/+和p53-/-细胞中的异位表达概括了最充分表征的p53效应，例如生长停滞、凋亡和分化。与在一半人类癌症中突变的p53不同，p73很少突变。然而，在神经母细胞瘤、肺癌、前列腺癌和肾细胞癌中已经报道了p73基因表达的改变。为了研究p73在急性髓性白血病（AML）中的潜在参与，我们分析了71例AML患者的N-末端反式激活-p73 α（TA-p73 α）、其剪接异构体和N-末端缺失-p73转录物（DeltaN-p73）的表达模式。我们检测到p73基因表达的AML FAB（法国-美国-英国）亚型无关。值得注意的是，DeltaN-p73表达的分析揭示了一种相当特殊的模式，该分析已被报道为抑制p53和p73的抗肿瘤作用。事实上，在27/28例（96.4%）M0、M1、M2、M4、M5和M6 AML病例中可检测到DeltaN-p73转录本和蛋白，在13/41例（31.7%）PML-RAR α阳性M3 AML病例中可检测到DeltaN-p73转录本和蛋白（P
p73, the homologue of p53, is a nuclear protein whose ectopic expression, in p53+/+ and p53-/- cells, recapitulates the most well-characterized p53 effects, such as growth arrest, apoptosis and differentiation. Unlike p53, which is mutated in half of human cancers, p73 is rarely mutated. However, altered expression of the p73 gene has been reported in neuroblastoma, lung cancer, prostate cancer and renal cell carcinoma. To investigate the potential involvement of p73 in acute myeloid leukemias (AMLs), we analyzed 71 samples from AML patients for the expression pattern of N-terminal transactivation-p73alpha (TA-p73alpha), its spliced isoforms and N-terminal-deleted-p73 transcripts (DeltaN-p73). We detected p73 gene expression in AML irrespective of FAB (French-American-British) subtypes. Notably, the analysis of DeltaN-p73 expression, which has been reported to inactivate both p53 and p73 antitumor effects, revealed a rather peculiar pattern. In fact, DeltaN-p73 transcript and protein were detectable in 27/28 (96.4%) cases of M0, M1, M2, M4, M5 and M6 AML and in 13/41 (31.7%) cases of PML-RARalpha-positive M3 AML (P