Dong L, Guo M, Huang S M, Jia S Q, Wang H
Department of Hematology, Institute of Basic Medical Sciences, Beijing, People's Republic of China.
Acta Haematol. 1999;101(3):119-23. doi: 10.1159/000040936.
To investigate the clinical implications of germline C mu transcription, the splice region between the 3' end of the enhancer and the first exon of immunoglobulin germline mu; was analyzed by RT-PCR in 63 samples from 59 patients with leukemia. Immunophenotypes of 33 samples from patients with acute leukemia were analyzed using a panel of these monoclonal antibodies: anti-immature/stem cell (HLA-DR, CD34); anti-mature myeloid (CD33, CD15); anti-T lymphoid (CD2, CD3, CD5, CD7, CD8), and anti-B lymphoid (CD10, CD19, CD20). Of the 63 samples, 33 (52%) contained germline C mu transcripts: 2/2 patients with chronic lymphocytic leukemia; 17/26 (65.4%) patients with acute myeloblastic leukemia; all 4 patients with chronic myelogenous leukemia in blast crisis and 1 in accelerated phase; 9/12 patients with acute lymphocytic leukemia. A clear correlation between germline transcripts and HLA-DR expression was observed among germline-positive cases (p < 0. 01). C mu expression and response to therapy clearly indicated that germline-mu-positive leukemia patients responded poorly to chemotherapy and had a worse clinical prognosis compared with C mu-negative patients (p < 0.01). After two courses of chemotherapy, 7/9 C mu-negative patients achieved complete remission compared to only 7/29 C mu-positive patients (p < 0.01). We conclude that the gene-regulating immunoglobulin germline C mu may be amplified in myeloid and B-lymphoid cells during leukemogenesis. Such genetic changes may be correlated with cellular terminal differentiation injury, resistance to chemotherapy and uncontrolled malignant cell proliferation.
为研究种系Cμ转录的临床意义，采用逆转录聚合酶链反应（RT-PCR）分析了59例白血病患者63份样本中增强子3'端与免疫球蛋白种系μ第一外显子之间的剪接区域。使用一组单克隆抗体分析了33例急性白血病患者样本的免疫表型：抗未成熟/干细胞（HLA-DR、CD34）；抗成熟髓系（CD33、CD15）；抗T淋巴细胞（CD2、CD3、CD5、CD7、CD8）和抗B淋巴细胞（CD10、CD19、CD20）。在63份样本中，33份（52%）含有种系Cμ转录本：2例慢性淋巴细胞白血病患者中的2例；26例急性髓细胞白血病患者中的17例（65.4%）；4例急变期慢性粒细胞白血病患者全部以及1例加速期患者；12例急性淋巴细胞白血病患者中的9例。在种系阳性病例中观察到种系转录本与HLA-DR表达之间存在明显相关性（p<0.01）。Cμ表达和对治疗的反应清楚地表明，与Cμ阴性患者相比，种系μ阳性白血病患者对化疗反应较差，临床预后更差（p<0.01）。两个疗程化疗后，9例Cμ阴性患者中的7例达到完全缓解，而Cμ阳性患者中只有29例中的7例（p<0.01）。我们得出结论，在白血病发生过程中，调节免疫球蛋白种系Cμ的基因可能在髓系和B淋巴细胞中扩增。这种基因变化可能与细胞终末分化损伤、化疗耐药和恶性细胞增殖失控有关。
