Yen C C, Liu J H, Wang W S, Fan F S, Chiou T J, Tai C J, Yang M H, Chao T C, Hsiao L T, Chen P M
Section of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
Zhonghua Yi Xue Za Zhi (Taipei). 2000 Nov;63(11):785-91.
Chronic myelogenous leukemia (CML) may transform into blast crisis (BC) if not properly treated. Among patients with transformation, 20% to 30% will develop BC with lymphoid-associated antigens (Ly-BC), and the remaining cases with myeloid-associated antigens (My-BC) or with both (Mix-BC). In this study, we investigated the lineage of blast cells in CML-BC using immunophenotypic and genetic analyses and analyzed the prognostic significance of genotypic change in CML-BC.
Twenty-one patients with CML-BC diagnosed at the Taipei Veterans General Hospital from 1982 to 1992 were included. Immunophenotyping was done by using the avidin-biotin immunoperoxidase technique. Genetic analyses were carried out by using Southern Blot hybridization. The prognostic influence of genotypic change was analyzed.
Thirteen patients (61.9%) expressed myeloid-associated antigens, one patient (4.8%) expressed megakaryoblast-associated antigens, four patients (19%) expressed B lymphoid-associated antigens and three patients (14.3%) expressed both myeloid and B lymphoid antigens. Clonal rearrangement of the immunoglobulin heavy chain (IgH) gene was found in six cases. Among them, four expressed B lymphoid markers only and two expressed both myeloid and B lymphoid markers. Patients with clonal IgH gene rearrangement tended to have a better response to chemotherapy (50% vs 8.3%, p = 0.08) and significantly longer survival (median survival, 5 months vs 3 months, p < 0.05) than did those with a germline configuration.
Clonal rearrangement of the IgH gene was found mostly in cases of Ly-BC and Mix-BC. We found that CML-BC with clonal rearrangement of the IgH gene had a more favorable prognosis than in cases with a germline configuration.
慢性粒细胞白血病（CML）若未得到恰当治疗可能会转化为急变期（BC）。在发生转化的患者中，20%至30%会发展为伴有淋巴系相关抗原的急变期（Ly-BC），其余病例则为伴有髓系相关抗原的急变期（My-BC）或两者皆有的混合急变期（Mix-BC）。在本研究中，我们运用免疫表型和基因分析方法研究了CML-BC中原始细胞的谱系，并分析了CML-BC基因型改变的预后意义。
纳入1982年至1992年在台北荣民总医院诊断为CML-BC的21例患者。采用抗生物素蛋白-生物素免疫过氧化物酶技术进行免疫表型分析。运用Southern印迹杂交进行基因分析。分析基因型改变的预后影响。
13例患者（61.9%）表达髓系相关抗原，1例患者（4.8%）表达巨核母细胞相关抗原，4例患者（19%）表达B淋巴系相关抗原，3例患者（14.3%）同时表达髓系和B淋巴系抗原。6例患者发现免疫球蛋白重链（IgH）基因的克隆性重排。其中，4例仅表达B淋巴系标志物，2例同时表达髓系和B淋巴系标志物。与具有种系构型的患者相比，具有IgH基因克隆性重排的患者对化疗的反应倾向于更好（50%对8.3%，p = 0.08），生存期显著更长（中位生存期，5个月对3个月，p < 0.05）。
IgH基因的克隆性重排多见于Ly-BC和Mix-BC病例。我们发现，具有IgH基因克隆性重排的CML-BC比具有种系构型的病例预后更良好。
