Nakagawa H, Fujii H, Nakai H, Inazawa J, Misawa S
Kyoto First Red Cross Hospital, Japan.
Am J Hematol. 1994 Apr;45(4):335-40. doi: 10.1002/ajh.2830450412.
We report a 64-year-old Japanese man with chronic myelogenous leukemia (CML) who expired with myelomonocytic crisis. Cytogenetic analyses of chronic phase (CP) and accelerated phase (AP) cells revealed a Philadelphia chromosome and an isochromosome for the long arm of chromosome 17, i(17q). This karyotype was replaced by another karyotype in blast crisis (BC), resulting in near triploidy with t(5;17) (p15;p11) and loss of chromosome 17 pter-->p11. Interphase fluorescent in situ hybridization studies with a chromosome 17 specific alpha satellite DNA probe confirmed the presence of a clonal change in BC. In addition, single-strand conformation polymorphism analysis and PCR-direct sequencing of BC cells revealed a point mutation at codon 203 of the p53 gene, GTG to GAG (Val to Glu), and loss of the normal allele. In contrast, no alterations of the p53 gene were found in CP and AP cells. Therefore, progression of CML in this patient appeared to be related to loss of 17p, as well as a mutation in the p53 gene.
我们报告一名64岁的日本慢性粒细胞白血病（CML）男性患者，其死于骨髓单核细胞危象。对慢性期（CP）和加速期（AP）细胞进行的细胞遗传学分析显示有费城染色体和17号染色体长臂等臂染色体，即i(17q)。此核型在急变期（BC）被另一种核型取代，导致近三倍体，伴有t(5;17) （p15;p11）和17号染色体短臂pter→p11缺失。使用17号染色体特异性α卫星DNA探针进行的间期荧光原位杂交研究证实了急变期存在克隆性改变。此外，对急变期细胞进行的单链构象多态性分析和PCR直接测序显示p53基因第203密码子发生点突变，由GTG变为GAG（缬氨酸变为谷氨酸），且正常等位基因缺失。相比之下，在慢性期和加速期细胞中未发现p53基因改变。因此，该患者慢性粒细胞白血病的进展似乎与17p缺失以及p53基因突变有关。
