Soekarman D, van Denderen J, Hoefsloot L, Moret M, Meeuwsen T, van Baal J, Hagemeijer A, Grosveld G
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Leukemia. 1990 Jun;4(6):397-403.
Two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia showed novel variants of the chimeric bcr-abl mRNA. The bcr-abl breakpoint region on cDNA derived from the chimeric mRNA was amplified using the polymerase chain reaction (PCR). Sequence analysis of the breakpoint-containing fragment showed that in both patients exon a2 of the abl gene was deleted, giving rise to an in-frame joining at the mRNA level of 5' bcr sequences to the abl exon a3. These findings were confirmed by Southern blot analysis and cloning of chromosomal DNA. Protein studies showed a bcr-abl protein with heightened tyrosine kinase activity in blast cells of both patients: one of the P190 type, the other of the P210 type. The significance of these findings and the role of this new type of translocation in the disregulation of the abl gene are discussed.
两名费城染色体阳性急性淋巴细胞白血病患者显示出嵌合型bcr-abl mRNA的新型变体。使用聚合酶链反应（PCR）扩增源自嵌合mRNA的cDNA上的bcr-abl断裂点区域。对含断裂点片段的序列分析表明，两名患者的abl基因外显子a2均缺失，导致5'bcr序列在mRNA水平与abl外显子a3发生读框内连接。这些发现通过Southern印迹分析和染色体DNA克隆得到证实。蛋白质研究显示，两名患者的原始细胞中bcr-abl蛋白的酪氨酸激酶活性增强：一名为P190型，另一名为P210型。讨论了这些发现的意义以及这种新型易位在abl基因失调中的作用。
