Westbrook C A, Le Beau M M, Diaz M O, Groffen J, Rowley J D
Proc Natl Acad Sci U S A. 1985 Dec;82(24):8742-6. doi: 10.1073/pnas.82.24.8742.
Acute nonlymphocytic leukemia associated with the chromosomal translocation t(6;9)(p23;q34) is an entity that is frequently associated with basophilia, which it shares with chronic myelogenous leukemia. The breakpoint on chromosome 9, q34, appears to be cytogenetically identical in both malignancies and is the site of the cellular oncogene c-abl. We investigated the role of c-abl in cells from two patients with the t(6;9) using in situ chromosomal hybridization, Southern hybridization, and in vitro phosphorylation. We showed that c-abl is not translocated from chromosome 9, resulting in a breakpoint that is on the 3' side of this gene. The t(6;9) translocation does not appear to result in the production of an aberrantly sized protein product or in the acquisition of in vitro tyrosine kinase activity. This is in direct contrast to the findings in chronic myelogenous leukemia, in which c-abl is translocated, leading to the production of a structurally altered c-abl protein with activated tyrosine kinase. Lastly, we demonstrated that the cells of one patient contain sequences from chromosome 9 inserted at the junction of a reciprocal translocation between chromosomes 4 and 10 on the 4q+ chromosome. This insertion, which is at least 100 kilobase pairs in length, represents a duplication and translocation of the protein coding region of c-abl.
与染色体易位t(6;9)(p23;q34)相关的急性非淋巴细胞白血病是一种常与嗜碱性粒细胞增多相关的疾病实体，慢性粒细胞白血病也有此表现。在这两种恶性肿瘤中，9号染色体q34处的断点在细胞遗传学上似乎是相同的，并且是细胞癌基因c-abl的位点。我们使用原位染色体杂交、Southern杂交和体外磷酸化方法，研究了c-abl在两名患有t(6;9)的患者细胞中的作用。我们发现c-abl并未从9号染色体易位，断点位于该基因的3'端。t(6;9)易位似乎并未导致异常大小的蛋白质产物的产生，也未导致体外酪氨酸激酶活性的获得。这与慢性粒细胞白血病的研究结果形成直接对比，在慢性粒细胞白血病中，c-abl发生易位，导致产生具有激活酪氨酸激酶的结构改变的c-abl蛋白。最后，我们证明一名患者的细胞含有来自9号染色体的序列，该序列插入到4号染色体上4q+染色体上4号和10号染色体相互易位的连接处。这种长度至少为100千碱基对的插入代表了c-abl蛋白编码区的重复和易位。
