Mutations of the Kirsten-ras proto-oncogene in human preleukaemia
Mutations of the Kirsten-ras proto-oncogene in human preleukaemia
复制标题
人类白血病前期的 Kirsten-ras 原癌基因突变
作者：
E. Liu;B. Hjelle;R. Morgan;F. Hecht;J. Bishop
骨髓增生异常综合征（MDS）或白血病前期是一种血液学疾病，其特征是血细胞计数低，骨髓细胞外观异常，多达30%的患者进展为急性白血病1。这种疾病独特的白血病前期和白血病阶段使其成为人类肿瘤肿瘤进展的一个有吸引力的模型。我们认为，由于显性转化基因（如ras原癌基因的突变等位基因）在急性白血病中如此频繁地发现，在MDS患者的临床过程中寻找这些遗传病变可能会让我们深入了解癌基因在白血病发生中的功能。我们在此报告了4例白血病前期患者中的2例，以及1例MDS进展为急性白血病的患者的骨髓细胞含有Ki-ras原癌基因的转化等位基因。在一名白血病前期患者中，在急性白血病发生前1.5年采集的骨髓细胞中检测到ras基因密码子13的新突变。我们的发现提供了ras突变可能参与人类白血病早期阶段的证据。
The myelodysplastic syndrome (MDS) or preleukaemia is a haematological disorder characterized by low blood counts, bone marrow cells of abnormal appearance and progression to acute leukaemia in as many as 30% of patients1. The distinctive pre-leukaemic and leukaemic phases of this disease make it an attractive model for neoplastic progression in human tumours. We reasoned that, because dominantly transforming genes (such as mutant alleles of ras proto-oncogenes) are found so frequently in acute leukaemia2, the search for these genetic lesions during the clinical course of patients with MDS might give us insight into the function of oncogenes in leukaemogenesis. We report here that bone marrow cells from two of four patients with preleukaemia, and from one patient who progressed to acute leukaemia from MDS, contained a transforming allele of the Ki-ras proto-oncogene. In one preleukaemic patient, a novel mutation in codon 13 of this ras gene was detected in bone marrow cells harvested 1.5 years before the acute leukaemia developed. Our findings provide evidence that ras mutations may be involved in the early stages of human leukaemia.