Rudolph Cornelia, Hegazy Ahmed N, von Neuhoff Nils, Steinemann Doris, Schröck Evelin, Stripecke Renata, Klein Christoph, Schlegelberger Brigitte
Institute of Cell and Molecular Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Cancer Genet Cytogenet. 2005 Aug;161(1):51-6. doi: 10.1016/j.cancergencyto.2004.12.021.
Most patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL) show evidence of secondary chromosome aberrations that may influence the course of disease and response to treatment. To better understand how these secondary chromosomal aberrations occur and to investigate whether the p185/p190 BCR-ABL fusion protein may directly induce an increased chromosomal instability and subsequently the appearance of clonal chromosome aberrations, three BRC-ABL (p185/ p190)-transduced mouse pre-B cell lines were analyzed by spectral karyotyping and fluorescence in situ hybridization. The human wild-type BCR-ABL gene was expressed at a level comparable with that in human Ph-positive leukemias at diagnosis. All BCR-ABL-transduced cell lines acquired similar clonal chromosomal aberrations. Trisomy 5 was always present, followed by loss of the Y chromosome, trisomy of chromosomes 12 and 18, and an unbalanced translocation between chromosomes X and 12. Thus, ectopic p185/p190 BCR-ABL expression, such as p210 BCR-ABL, PML-RARA, or C-MYC transduction, may induce an increased chromosomal instability leading to clonal karyotypic evolution, which may mimic secondary chromosome aberrations in human Ph-positive ALL.
大多数费城（Ph）阳性急性淋巴细胞白血病（ALL）患者显示出继发性染色体畸变的证据，这些畸变可能影响疾病进程和对治疗的反应。为了更好地理解这些继发性染色体畸变是如何发生的，并研究p185/p190 BCR-ABL融合蛋白是否可能直接诱导染色体不稳定性增加，进而导致克隆性染色体畸变的出现，通过光谱核型分析和荧光原位杂交对三种BRC-ABL（p185/p190）转导的小鼠前B细胞系进行了分析。人类野生型BCR-ABL基因的表达水平与人类Ph阳性白血病诊断时的水平相当。所有BCR-ABL转导的细胞系都获得了相似的克隆性染色体畸变。总是出现5号染色体三体，随后是Y染色体缺失、12号和18号染色体三体，以及X染色体和12号染色体之间的不平衡易位。因此，异位p185/p190 BCR-ABL表达，如p210 BCR-ABL、PML-RARA或C-MYC转导，可能会诱导染色体不稳定性增加，导致克隆核型进化，这可能模拟人类Ph阳性ALL中的继发性染色体畸变。
