Cogswell P C, Morgan R, Dunn M, Neubauer A, Nelson P, Poland-Johnston N K, Sandberg A A, Liu E
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Blood. 1989 Dec;74(8):2629-33.
Seventy cases of chronic myelogenous leukemia (CML) were analyzed for the presence of ras mutations using polymerase chain reaction (PCR), oligonucleotide hybridization, and direct PCR sequencing. All cases had preceding cytogenetic and bcr rearrangement studies. Aberrant ras genes were detected in none of 39 patients with Philadelphia (Ph) chromosome or bcr/abl rearrangement positive chronic-phase CML and in only 1 of 18 patients in blast crisis, suggesting that ras mutations have little or no role in initiation or progression of common CML. Seven of 13, or 54% of patients with bcr/abl rearrangement negative chronic phase CML (atypical CML) harbored mutations in ras, however. This high incidence of ras mutations, together with the absence of bcr/abl rearrangement, provides evidence that atypical CML is an entity that is molecularly distinct from common CML. Moreover, the clinical characteristics and the high frequency of ras mutations suggest that atypical CML may constitute a subset of the myelodysplastic syndrome and may be best classified as a variant of chronic myelomonocytic leukemia (CMML).
采用聚合酶链反应（PCR）、寡核苷酸杂交和直接PCR测序技术，对70例慢性粒细胞白血病（CML）患者进行ras突变检测。所有病例均先行细胞遗传学和bcr重排研究。在39例费城（Ph）染色体或bcr/abl重排阳性的慢性期CML患者中未检测到异常ras基因，在18例急变期患者中仅1例检测到，提示ras突变在常见CML的发生或进展中作用很小或无作用。然而，在13例bcr/abl重排阴性的慢性期CML（非典型CML）患者中，有7例（54%）存在ras突变。ras突变的高发生率以及bcr/abl重排的缺失，证明非典型CML是一种在分子水平上与常见CML不同的疾病实体。此外，临床特征和ras突变的高频率提示，非典型CML可能构成骨髓增生异常综合征的一个亚型，可能最好归类为慢性粒单核细胞白血病（CMML）的一个变异型。
