Rieder H, Ludwig W D, Gassmann W, Maurer J, Janssen J W, Gökbuget N, Schwartz S, Thiel E, Löffler H, Bartram C R, Hoelzer D, Fonatsch C
Department of Clinical Genetics, Medical Centre of Human Genetics, Philipps University, Marburg, Germany.
Br J Haematol. 1996 Dec;95(4):678-91. doi: 10.1046/j.1365-2141.1996.d01-1968.x.
The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD: 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.
在66例费城（Ph）染色体阳性成人急性淋巴细胞白血病（ALL）患者的大型队列中，研究了额外染色体畸变的临床和生物学意义。71%的病例观察到额外的染色体变化。26%的病例发现9号染色体异常，17%的病例同时发现7号染色体单体和超二倍体核型50。9号染色体异常的特征是完全缓解（CR）率低（58%）和中位缓解持续时间极短（MRD：100天）。7号染色体单体的患者治疗结果较差得到证实（CR率55%：MRD 113天）。相比之下，所有超二倍体核型50的患者均实现CR，总体生存率优于所有其他Ph阳性ALL患者，但无额外染色体畸变的患者除外。9号染色体异常病例中BCR基因小断裂点簇区域的排他性重排以及髓系相关抗原的共表达缺失，以及7号染色体单体患者中BCR基因大断裂点簇区域的高频重排（89%）进一步证实，额外的染色体畸变可能是Ph阳性ALL不同亚组的特征。此外，由于3%的病例存在变异Ph易位，4%的病例PCR检测呈阴性，因此在准确识别Ph阳性患者时，补充使用染色体显带分析、聚合酶链反应（PCR）检测和荧光原位杂交的必要性变得明显。
