Weissinger E M, Thalmeier K, Dull T, Grammer C, Kempkes B, Brielmeier M, Schumm M, Kolb H J
Institute for Clinical Hematology, GSF, National Research Institute for Environment and Health, Munich, Germany.
Int J Cancer. 1996 Nov 27;68(5):577-82. doi: 10.1002/(SICI)1097-0215(19961127)68:5<577::AID-IJC4>3.0.CO;2-W.
Chronic myelogenous leukemia is a disease of the pluripotent stem cell that involves the myeloid and, to a varying degree, the lymphoid compartment. We studied the involvement of B cells in chronic myelogenous leukemia at diagnosis and during treatment. B lymphocytes were immortalized by infection with Epstein-Barr virus. B-lymphoid cell lines could be established from 25 patients suffering from Philadelphia-chromosome (Ph1)-positive chronic myelogenous leukemia. The cell lines were tested for expression of the typical 210-kDa fusion protein, p210, using Western-blot analysis, and/or for mRNA expression of bcr-abl fusion genes, using reverse transcriptase polymerase chain reaction analysis. At diagnosis, mosaicism of B cells was demonstrated in every patient. During treatment with interferon alpha, p210-expressing B-lymphoid cell lines could not be established from 8 of 8 patients. Following discontinuation of IFN-alpha therapy, p210-positive cell lines were found early, even before cytogenetic recurrence. Resistance to IFN-alpha therapy and progression of the disease were both associated with the appearance of p210-positive cell lines. Cell lines established from 3 healthy individuals and from patients suffering from Ph1-negative diseases did not show p210 expression in Western blots. Our data suggest that B lymphocytes are involved early in the disease, and that B-cell mosaicism may be a sensitive marker for resistance to IFN-alpha therapy and disease progression.
慢性粒细胞白血病是一种多能干细胞疾病，累及髓系，并在不同程度上累及淋巴系。我们研究了慢性粒细胞白血病患者在诊断时及治疗期间B细胞的受累情况。通过感染爱泼斯坦-巴尔病毒使B淋巴细胞永生化。从25例费城染色体（Ph1）阳性的慢性粒细胞白血病患者中可建立B淋巴细胞系。使用蛋白质免疫印迹分析检测细胞系中典型的210 kDa融合蛋白p210的表达，和/或使用逆转录聚合酶链反应分析检测bcr-abl融合基因的mRNA表达。诊断时，每名患者均显示有B细胞镶嵌现象。在使用α干扰素治疗期间，8例患者中有8例无法建立表达p210的B淋巴细胞系。停用α干扰素治疗后，甚至在细胞遗传学复发之前就早早发现了p210阳性细胞系。对α干扰素治疗的耐药性和疾病进展均与p210阳性细胞系的出现有关。从3名健康个体和Ph1阴性疾病患者建立的细胞系在蛋白质免疫印迹中未显示p210表达。我们的数据表明，B淋巴细胞在疾病早期就受累，并且B细胞镶嵌现象可能是对α干扰素治疗耐药和疾病进展的敏感标志物。
