Thiel E, Kranz B R, Raghavachar A, Bartram C R, Löffler H, Messerer D, Ganser A, Ludwig W D, Büchner T, Hoelzer D
Department of Hematology and Oncology, Free University of Berlin, FRG.
Blood. 1989 Apr;73(5):1247-58.
Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T-cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.
作为一项前瞻性治疗方案研究的一部分，对739例成年急性淋巴细胞白血病（ALL）患者的预处理原始细胞进行了免疫表型分析。在192例（26%）T系ALL患者中，47例（6%；占T系ALL的24%）的原始淋巴细胞不形成绵羊红细胞花环，但细胞膜上有泛T抗原CD7，细胞内CD3蛋白大多呈核周聚集。T细胞表面抗原CD5和/或CD2以及酸性磷酸酶是这个传统上称为前T ALL亚组的额外标志物，而胸腺细胞抗原CD1以及CD4和CD8抗原未表达。造血祖细胞标志物，即末端脱氧核苷酸转移酶（TdT），部分还有常见ALL抗原（CD10）、HLA-DR抗原和/或My-10（CD34），后者是胸腺细胞中不存在的骨髓细胞独特抗原，进一步界定了这种具有假定原胸腺细胞表型的不成熟T-ALL形式（CD7+/细胞内CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-）。在分析的36例患者中的21例中发现的种系T细胞受体β基因支持了胸腺前T细胞特征。在5例中只有Tγ链基因发生重排。然而，15例患者的Tβ和Tγ基因均发生重排。免疫球蛋白重链基因仅在2例中发生重排。前T ALL在一些临床表现上与E花环阳性T-ALL有显著差异，即纵隔肿块、淋巴结病和血小板计数，并且在预后方面独立于临床因素（P = 0.02，中位缓解期：15.7对33.5个月，P = 0.02，中位生存时间：24.6对50.7个月）。我们得出结论，仅基于T或B细胞系归属的ALL分类是不够的，还需要根据相关成熟阶段进一步细分，如此处T细胞轴内所示例的那样。所描述的假定胸腺前T细胞祖细胞表型可能有助于阐明使正常造血细胞定向为T细胞系的遗传事件序列。
