Chan L C, Karhi K K, Rayter S I, Heisterkamp N, Eridani S, Powles R, Lawler S D, Groffen J, Foulkes J G, Greaves M F, Wiedemann L M
Nature. 1987;325(6105):635-7. doi: 10.1038/325635a0.
The Philadelphia (Ph) chromosome breakpoints in chronic myelocytic leukaemia are clustered on chromosome 22 band q11 in a 5.8-kilobase (kb) region designated bcr. The c-abl protooncogene is translocated from chromosome 9 band q34 into bcr and the biochemical consequence of this molecular rearrangement is the production of an abnormal fusion protein bcr-abl p210 with enhanced protein-tyrosine kinase activity compared to the normal p145 c-abl protein. The Ph chromosome translocation is also seen in some acute lymphoblastic leukaemias with B-cell precursor phenotypes some of which have bcr rearrangement (bcr+) and some do not (bcr-). We present evidence that the Ph+, bcr- leukaemias are associated with a novel p190 abl kinase. We propose that acute lymphoblastic leukaemias that are bcr+, p210+ are probably lymphoid blast crises following a clinically silent chronic phase of chronic myelocytic leukaemia arising in multipotential stem cells whereas bcr-, p190+ cases are de novo acute lymphoblastic leukaemias arising in more restricted precursors.
慢性粒细胞白血病中的费城（Ph）染色体断点聚集在22号染色体q11带的一个5.8千碱基（kb）的区域，该区域被命名为bcr。原癌基因c-abl从9号染色体q34带易位至bcr，这种分子重排的生化结果是产生一种异常融合蛋白bcr-abl p210，与正常的p145 c-abl蛋白相比，其蛋白酪氨酸激酶活性增强。在一些具有B细胞前体表型的急性淋巴细胞白血病中也可见到Ph染色体易位，其中一些伴有bcr重排（bcr+），一些则没有（bcr-）。我们提供的证据表明，Ph+、bcr-白血病与一种新的p190 abl激酶有关。我们提出，bcr+、p210+的急性淋巴细胞白血病可能是多能干细胞中慢性粒细胞白血病临床无症状慢性期后的淋巴母细胞危象，而bcr-、p190+的病例是由更局限的前体细胞产生的新发急性淋巴细胞白血病。
