Hirai H, Ishikawa F
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo.
Rinsho Ketsueki. 1991 Apr;32(4):319-26.
Chronic myelogenous leukemia (CML) is characterized cytogenetically by the presence of the Philadelphia chromosome, which is the result of a reciprocal translocation between chromosomes 9 and 22. Analysis of the rearranged chromosome 22 have demonstrated that the DNA breakpoints fall within a 5.8-kilobase (kb) region termed M-bcr. In Ph1-acute lymphocytic leukemia, approximately half of the patients have a breakpoint within M-bcr, whereas the remaining half have the break within the first intron of the BCR gene (m-bcr). We have investigated five cases with CML in the blastic phase to search the molecular mechanism of blastic crisis in CML. Using a method of reverse transcriptase-polymerase chain reaction (RT-PCR), we have identified both types of breakpoints in samples of the three cases, suggesting the existence of M-bcr/ABL and m-bcr/ABL chimeric mRNAs in the RNA samples derived from blasts of the three cases. We have further analysed for alterations in the p53 gene in those cases. The p53 gene is now considered to be a tumor suppressor gene and its mutations play a role in the development of many human malignancies. We have attempted to determine whether the p53 gene is involved in the mechanism of blastic crisis in CML. Using the methods of RT-PCR and single stand-conformational polymorphism (SSCP), we have detected expression of only a mutated p53 allele in a case with CML blastic crisis, indicating that inactivation of the p53 gene in both alleles may contribute to the blastic crisis in this case. Accumulation of molecular analysis in more cases will clarify the mechanism of blastic crisis in CML.
慢性粒细胞白血病（CML）在细胞遗传学上的特征是存在费城染色体，它是9号和22号染色体相互易位的结果。对重排的22号染色体的分析表明，DNA断点位于一个5.8千碱基（kb）的区域，称为M-bcr。在Ph1急性淋巴细胞白血病中，大约一半的患者在M-bcr内有断点，而其余一半在BCR基因的第一个内含子（m-bcr）内有断点。我们研究了5例处于急变期的CML患者，以探寻CML急变期的分子机制。使用逆转录聚合酶链反应（RT-PCR）方法，我们在3例患者的样本中鉴定出了两种类型的断点，提示在这3例患者原始细胞来源的RNA样本中存在M-bcr/ABL和m-bcr/ABL嵌合mRNA。我们进一步分析了这些病例中p53基因的改变。p53基因现在被认为是一种肿瘤抑制基因，其突变在许多人类恶性肿瘤的发生中起作用。我们试图确定p53基因是否参与CML急变期的机制。使用RT-PCR和单链构象多态性（SSCP）方法，我们在1例CML急变期患者中仅检测到一个突变的p53等位基因的表达，表明两个等位基因的p53基因失活可能促成了该病例的急变期。对更多病例进行分子分析将阐明CML急变期的机制。
