The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia.
The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia.
复制标题
慢性粒细胞白血病进化过程中的分子变化谱。
DOI：
10.1172/jci115234
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Cline,M
中科院分区：
文献类型：
--
作者：
Ahuja,H;Bar-Eli,M;Arlin,Z;Advani,S;Allen,SL;Goldman,J;Snyder,D;Foti,A;Cline,M
研究了135例不同临床阶段的慢性粒细胞白血病（CML）和费城（Ph1）染色体阳性的急性淋巴细胞白血病患者的DNA，研究了多种原癌基因的改变，这些基因与CML从慢性期向原细胞危象的演变有关。在典型的Ph1染色体阳性CML向胚危机的进化过程中，最常见的遗传变化是p53基因的改变，包括基因编码序列的重排、缺失或点突变。p53基因的改变在髓系和罕见的巨核细胞突变体中发现，但在淋巴系白血病转化体中没有发现。54例髓系或未知表型的细胞危象中有11例（20%）出现明显的结构改变，44例慢性期病例中仅有1例。在blast危重症患者中观察到8例p53基因开放阅读框密码子49、53、60、140、202、204、238和239处的突变。N-RAS基因突变在典型的母细胞危象中很少见（27例中有2例），但在巨核细胞危象和Ph1阴性的髓细胞危象中发现。我们得出结论，p53基因的异质改变和偶尔的N-RAS基因的改变伴随着慢性期CML向细胞危象的演变。图片
DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.Images