Stirewalt D L, Clurman B, Appelbaum F R, Willman C L, Radich J P
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98109, USA.
Leukemia. 1999 Jul;13(7):985-90. doi: 10.1038/sj.leu.2401418.
The p73 gene is a candidate tumor suppressor gene that has significant homology to p53. Thus far, p73 has not been investigated in hematopoietic malignancies. We used single-strand conformation polymorphism analysis to examine 60 de novo acute myelogenous leukemia (AML) patients for p73 mutations in exons 4, 6 and 7, which are homologous to the most frequently mutated exons in p53. Mutations were not found, but we did identify polymorphisms in exons 4 and 7. We also examined p73 RNA expression in 15 AML samples, eight cell lines, and eight normal bone marrows using the reverse transcriptase/polymerase chain reaction assay. All 31 RNA samples had p73 expression. Fourteen RNA samples were informative for allelic expression, being heterozygous for a polymorphism in codon 173 of exon 4. The two normal bone marrows and the K562 cell line had evidence of biallelic expression while six of 10 AML patients and the Kasumi (AML) cell line had monoallelic expression. These data suggest that functional p73 mutations in exons 4, 6 and 7 do not occur in most de novo AML patients. In addition, biallelic expression of p73 occurs in normal bone marrows, some AML samples, and specific cell lines. Lastly, monoallelic p73 expression appears to be common in de novo AML.
p73基因是一种候选肿瘤抑制基因，与p53具有显著的同源性。迄今为止，尚未在造血系统恶性肿瘤中对p73进行研究。我们使用单链构象多态性分析，检测了60例初发急性髓性白血病（AML）患者的第4、6和7外显子中的p73突变，这些外显子与p53中最常发生突变的外显子同源。未发现突变，但我们确实在第4和7外显子中鉴定出了多态性。我们还使用逆转录酶/聚合酶链反应检测法，检测了15例AML样本、8种细胞系和8例正常骨髓中的p73 RNA表达。所有31个RNA样本均有p73表达。14个RNA样本对于等位基因表达具有信息价值，它们在第4外显子密码子173处存在多态性的杂合状态。2例正常骨髓和K562细胞系有双等位基因表达的证据，而10例AML患者中的6例以及Kasumi（AML）细胞系有单等位基因表达。这些数据表明，大多数初发AML患者的第4、6和7外显子中不存在功能性p73突变。此外，p73的双等位基因表达在正常骨髓、一些AML样本和特定细胞系中出现。最后，单等位基因p73表达在初发AML中似乎很常见。
