Marasca R, Longo G, Luppi M, Barozzi P, Torelli G
Center for Experimental Hematology, University of Modena, Italy.
Leuk Lymphoma. 1994 Dec;16(1-2):171-5. doi: 10.3109/10428199409114155.
A patient with Philadelphia-positive chronic myelogenous leukemia (CML) evolved in extramedullary blast crisis, was studied for the presence of alterations of the P53 tumor suppressor gene in the different stages of disease progression. No P53 gene aberrations were detected during the chronic and accelerated phases. Two identical missense point mutations, involving codons 249 and 281 and leading to the amino acid substitutions Arg-Ser and Thy-Asp, were identified in cells of an extramedullary mass and then in peripheral blood blast crisis cells. The data indicate that the medullary and extramedullary blast cells belong to the same cellular clone. They also strongly suggest that in this case, the alteration of P53 gene is strictly related to the progression of the disease, although this mechanism is certainly neither the only nor the most frequent molecular event leading to the acute phase.
一名费城染色体阳性的慢性髓性白血病（CML）患者发展为髓外原始细胞危象，对其疾病进展不同阶段中P53肿瘤抑制基因的改变情况进行了研究。在慢性期和加速期未检测到P53基因畸变。在一个髓外肿块的细胞中，随后又在外周血原始细胞危象细胞中，鉴定出两个相同的错义点突变，涉及密码子249和281，导致氨基酸替换为精氨酸-丝氨酸和苏氨酸-天冬氨酸。数据表明，髓内和髓外原始细胞属于同一细胞克隆。它们还强烈提示，在这种情况下，P53基因的改变与疾病进展密切相关，尽管这一机制肯定既不是导致急性期的唯一分子事件，也不是最常见的分子事件。
