Lichty B D, Keating A, Callum J, Yee K, Croxford R, Corpus G, Nwachukwu B, Kim P, Guo J, Kamel-Reid S
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario Cancer Institute, Princess Margaret Hospital, Canada.
Br J Haematol. 1998 Dec;103(3):711-5. doi: 10.1046/j.1365-2141.1998.01033.x.
The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusion protein, p210. Patients with CML in blast crisis, or with Philadelphia positive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fusion transcript possessing only the first exon of BCR fused to ABL. This smaller transcript encodes a 190 kD protein which is more strongly transforming than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and found that 35 of them expressed both transcripts whereas the remainder expressed the p210-encoding transcript exclusively. Additional PCR products of an intermediate size were also frequently detected and have been isolated and sequenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CML is also due to alternative splicing. A comparison of patients co-expressing the p190- and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly higher white blood cell (WBC) counts and blast cell counts at time of testing as well as significantly higher white blood cell counts at diagnosis.
慢性粒细胞白血病（CML）的标志是存在费城染色体及其产生的融合信息BCR-ABL和融合蛋白p210。处于急变期的CML患者，或费城染色体阳性的急性淋巴细胞白血病（ALL）患者，可能有一个较小的BCR-ABL融合转录本，仅包含与ABL融合的BCR的第一个外显子。这个较小的转录本编码一种190 kD的蛋白，其转化能力比源自较大的CML相关转录本的p210蛋白更强。我们对慢性期CML患者的样本进行了逆转录聚合酶链反应（RT-PCR），以确定p190和p210共表达的频率和机制，并观察这是否与临床指标相关。我们检查了67例CML患者的外周血或骨髓，发现其中35例同时表达两种转录本，而其余患者仅表达编码p210的转录本。还经常检测到中等大小的额外PCR产物，并已对其进行分离和测序。其中两种产物的数据表明它们是可变剪接的结果，包括BCR外显子的可变组合。我们认为CML慢性期编码p190的转录本的表达也是由于可变剪接。将同时表达编码p190和p210转录本的患者与仅表达编码p210转录本的患者进行比较，发现在检测时前者的白细胞（WBC）计数和原始细胞计数显著更高，在诊断时白细胞计数也显著更高。
