Wuchter C, Harbott J, Schoch C, Schnittger S, Borkhardt A, Karawajew L, Ratei R, Ruppert V, Haferlach T, Creutzig U, Dörken B, Ludwig W D
Department of Hematology, Oncology and Tumor Immunology, Robert-Rössle Clinic, Charité, Humboldt-University Berlin, Germany.
Leukemia. 2000 Jul;14(7):1232-8. doi: 10.1038/sj.leu.2401840.
Translocations involving 11q23 are among the most common genetic abnormalities in hematologic malignancies, occurring in approximately 5-10% of acute lymphoblastic leukemia (ALL) and 5% of acute myeloblastic leukemia (AML). In 11q23 translocations, the mixed lineage leukemia (MLL) gene on chromosome 11, band q23, is usually disrupted. The human homologue of the rat NG2 chondroitin sulfate proteoglycan molecule, as detected by the monoclonal antibody (moab) 7.1, was shown to be expressed on leukemic cells with MLL rearrangements of children with acute leukemia. We further investigated the reactivity of the moab 7.1 on 533 cell samples of adults (n = 215) and children (n = 318) with acute leukemias (271 AML, 217 B-lineage ALL, 37 T-lineage ALL, eight CD7+ CD56+ myeloid/natural killer cell precursor acute leukemias) by flow cytometry. In AML, 38 samples were positive for moab 7.1 ('20%-cut-off-level'). These moab 7.1-positive AML cases revealed a myelomonocytic-differentiated immunophenotype with coexpression of the NK cell marker CD56 in 33 of 38 cases. Two of eight cell samples of the recently described CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia entity reacted with moab 7.1. In ALL, 35 samples mostly of the pro-B-ALL subtype (33 pro-B-ALL, one common-ALL, one pre-B-ALL) were positive for moab 7.1. 58 (81%) of 72 samples with MLL rearrangements were positive for moab 7.1 including 28/31 with a t(4;11), 16/17 with a t(9;11), 3/5 with a t(11;19), and 2/6 with a del(11)(q23). All moab 7.1-positive ALL (n = 34) and childhood AML (n = 17) cases revealed MLL rearrangements as detected by Southern blot analysis and RT-PCR. However, 11 adults with AML, and one adult with moab 7.1-positive CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia were negative for MLL rearrangements as proved by Southern blot analysis. We conclude that moab 7.1 is a sensitive but not entirely specific marker for the identification of 11q23-associated AML and ALL by flow cytometry in children and adults.
涉及11q23的易位是血液系统恶性肿瘤中最常见的基因异常之一，约5% - 10%的急性淋巴细胞白血病（ALL）和5%的急性髓细胞白血病（AML）会出现这种情况。在11q23易位中，11号染色体q23带的混合谱系白血病（MLL）基因通常会被破坏。用单克隆抗体（moab）7.1检测到的大鼠NG2硫酸软骨素蛋白聚糖分子的人类同源物，在患有急性白血病的儿童的白血病细胞上有表达，这些白血病细胞具有MLL重排。我们通过流式细胞术进一步研究了moab 7.1对533例成人（n = 215）和儿童（n = 318）急性白血病细胞样本（271例AML、217例B系ALL、37例T系ALL、8例CD7 + CD56 + 髓系/自然杀伤细胞前体急性白血病）的反应性。在AML中，38个样本moab 7.1呈阳性（“20% - 临界值”）。这些moab 7.1阳性的AML病例显示出一种髓单核细胞分化的免疫表型，38例中有33例同时表达NK细胞标志物CD56。最近描述的CD7 + CD56 + 髓系/自然杀伤细胞前体急性白血病实体的8个细胞样本中有2个与moab 7.1反应。在ALL中，35个样本大多为前B - ALL亚型（33例前B - ALL、1例普通ALL、1例前B - ALL）moab 7.1呈阳性。72例有MLL重排的样本中有58例（81%）moab 7.1呈阳性，包括28/31例t(4;11)、16/17例t(9;11)、3/5例t(11;19)和2/6例del(11)(q23)。所有moab 7.1阳性的ALL（n = 34）和儿童AML（n = 17）病例经Southern印迹分析和RT - PCR检测均显示有MLL重排。然而，Southern印迹分析证明，11例成人AML患者以及1例moab 7.1阳性的CD7 + CD56 + 髓系/自然杀伤细胞前体急性白血病成人患者MLL重排为阴性。我们得出结论，moab 利用流式细胞术鉴定儿童和成人中与11q23相关的AML和ALL时，moab 7.1是一个敏感但并非完全特异的标志物。
