Rovira A, Urbano-Ispizua A, Cervantes F, Rozman M, Vives-Corrons J L, Montserrat E, Rozman C
Postgraduate School of Hematology, Hematology Department, Hospital Clínic i Provincial, Barcelona, Spain.
Ann Hematol. 1995 Mar;70(3):129-33. doi: 10.1007/BF01682032.
Loss of the p53 gene alleles was investigated in 26 patients with Ph+, BCR/ABL+ chronic myeloid leukemia (CML) by means of the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis using the restriction enzyme AccII. In all cases, peripheral blood and/or bone marrow samples were obtained at different times during the chronic phase of the disease and at blast crisis, and in some of them also at the accelerated phase. Of the 12 cases considered informative, 11 evolved into myeloid type blast crisis and one into a lymphoid blast crisis, whereas only two showed an i(17q) chromosome at cytogenetic study. In four of the 12 informative cases, a loss of one p53 gene allele was observed, in all cases coincident with the development of the accelerated phase or blast crisis. One patient with a deleted p53 gene allele, in whom it was possible to analyze the gene structure in the three CML evolutive phases (chronic and accelerated phases and blast crisis), showed loss of the p53 gene allele in both the accelerated and the blastic phase, but not during the chronic phase. On the other hand, one of the two cases with an i(17q) chromosome exhibited one allelic deletion of the p53 gene. Thus, the relatively frequent monoallelic deletion of the p53 gene coincident with the appearance of the blast crisis registered in the present study would support a possible role of the p53 gene alterations in the evolution of CML to its final stages.
采用聚合酶链反应和限制性片段长度多态性分析（PCR-RFLP），使用限制性内切酶AccII，对26例Ph+、BCR/ABL+慢性髓性白血病（CML）患者的p53基因等位基因缺失情况进行了研究。在所有病例中，于疾病慢性期的不同时间以及急变期采集外周血和/或骨髓样本，部分病例还在加速期采集了样本。在12例具有信息价值的病例中，11例演变为髓系急变期，1例演变为淋巴系急变期，而细胞遗传学研究仅发现2例存在i(17q)染色体。在12例具有信息价值的病例中，有4例观察到一个p53基因等位基因缺失，所有这些病例均与加速期或急变期的发生同时出现。有1例p53基因等位基因缺失的患者，能够对CML的三个演变阶段（慢性期、加速期和急变期）的基因结构进行分析，结果显示在加速期和急变期均出现了p53基因等位基因缺失，但在慢性期未出现。另一方面，2例具有i(17q)染色体的病例中有1例出现了p53基因的一个等位基因缺失。因此，本研究中观察到的p53基因相对频繁的单等位基因缺失与急变期的出现同时发生，这支持了p53基因改变在CML向终末期演变过程中可能发挥作用的观点。
