Imamura N, Kuramoto A, Ishihara H, Shimizu S
Department of Internal Medicine, Hiroshima University, Japan.
Am J Hematol. 1993 Jun;43(2):151-3. doi: 10.1002/ajh.2830430217.
We have been analyzing RAS p21 proteins and the DNA sequence of leukemic cells. We report here that these cells have high expression of H-RAS p21, which originates from point mutations of RAS oncogenes. The leukemic cells from six patients with acute myelogenous leukemia were separated from heparinized whole blood and bone marrow by a density gradient technique. The expression of RAS oncogenes was analyzed by a fluorescence-activated cell sorting with a panel of monoclonal antibodies. The high expression of DWP, which was reported to recognized activated RAS oncogene, was found in two patients and was associated with high levels of H-RAS expression. These facts prompted us to analyze the DNA sequence of RAS genes with an automated DNA sequencer. Unexpectedly, various kinds of H-RAS point mutations were found in all six cases, including two cases of hot-spot point mutation at codon 12, whereas K-RAS point mutation (no hot-spot point mutations) was found in six cases. The same H-RAS point mutations, at codons 10, 11, and 15, were found in all six cases. To our knowledge, there is no report on H-RAS point mutation in human leukemias. On the basis of these findings, we suggest that H-RAS point mutation together with p53 gene mutation may play an important role in leukemogenesis.
我们一直在分析RAS p21蛋白和白血病细胞的DNA序列。我们在此报告，这些细胞具有高表达的H-RAS p21，其源于RAS癌基因的点突变。通过密度梯度技术从肝素化全血和骨髓中分离出6例急性髓性白血病患者的白血病细胞。用一组单克隆抗体通过荧光激活细胞分选分析RAS癌基因的表达。在两名患者中发现了据报道可识别活化RAS癌基因的DWP的高表达，并且其与高水平的H-RAS表达相关。这些事实促使我们用自动DNA测序仪分析RAS基因的DNA序列。出乎意料的是，在所有6例病例中均发现了各种类型的H-RAS点突变，包括2例密码子12处的热点突变，而在6例病例中发现了K-RAS点突变（无热点突变）。在所有6例病例中均发现了密码子10、11和15处相同的H-RAS点突变。据我们所知，尚无关于人类白血病中H-RAS点突变的报道。基于这些发现，我们认为H-RAS点突变与p53基因突变可能在白血病发生中起重要作用。
