Kurzrock R, Shtalrid M, Talpaz M, Kloetzer W S, Gutterman J U
Department of Clinical Immunology, M.D. Anderson Hospital and Tumor Institute at Houston, TX 77030.
Blood. 1987 Nov;70(5):1584-8.
The identical cytogenetic marker, t(9;22)(q34;q11) (Philadelphia [Ph] translocation), is found in approximately 90%, 20%, and 2% of adult patients with chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML), respectively. In CML, the molecular events resulting from the Ph translocation include a break within the bcr locus on chromosome 22, transfer of the c-abl protooncogene from chromosome 9 to 22, and formation of an aberrant 210-kD bcr-abl fusion protein (p210bcr-abl). Recently, the absence of bcr rearrangement and expression of a distinct aberrant 190-kd abl protein (p190c-abl) has been described in Ph-positive ALL, with the suggestion that the two abl variants may be pathogenetically associated with myeloid v lymphoid leukemogenesis. Here we report that the genomic configuration and translation product of Ph-positive AML can be similar to that of Ph-positive ALL: the break at 22q11 may occur outside the 5.8 kb bcr region and result in expression of a 190-kD abl protein lacking these bcr sequences. Phosphokinase enzymatic activity, a fundamental property of p210bcr-abl, was also associated with AML-derived p190c-abl. Our current observations indicate that p190c-abl can be found in cells of lymphoid or myeloid lineage and is therefore unlikely to play a specific role in the development of lymphoid leukemias. Formation of p190c-abl instead of p210bcr-abl appears to be a characteristic of the acute rather than the chronic Ph-positive leukemic state.
相同的细胞遗传学标记，即t(9;22)(q34;q11)（费城[Ph]易位），分别在约90%的成年慢性髓性白血病（CML）患者、20%的急性淋巴细胞白血病（ALL）患者和2%的急性髓性白血病（AML）患者中被发现。在CML中，Ph易位导致的分子事件包括22号染色体上bcr基因座内的断裂、c-abl原癌基因从9号染色体转移至22号染色体，以及形成异常的210-kD bcr-abl融合蛋白（p210bcr-abl）。最近，在Ph阳性ALL中已发现不存在bcr重排且表达一种独特的异常190-kd abl蛋白（p190c-abl），这表明这两种abl变体可能在发病机制上与髓系和淋巴系白血病发生相关。在此我们报告，Ph阳性AML的基因组结构和翻译产物可能与Ph阳性ALL相似：22q11处的断裂可能发生在5.8 kb bcr区域之外，并导致缺乏这些bcr序列的190-kD abl蛋白的表达。磷酸激酶酶活性是p210bcr-abl的一项基本特性，它也与AML来源的p190c-abl相关。我们目前的观察结果表明，p190c-abl可在淋巴系或髓系细胞谱系中发现，因此不太可能在淋巴系白血病的发生中发挥特定作用。形成p190c-abl而非p210bcr-abl似乎是急性而非慢性Ph阳性白血病状态的一个特征。
