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儿童急性淋巴细胞白血病细胞上髓系抗原表达的测定:使用不同单克隆抗体克隆的差异

Determination of myeloid antigen expression on childhood acute lymphoblastic leukaemia cells: discrepancies using different monoclonal antibody clones.

作者信息

Firat H, Favier R, Adam M, Leverger G, Landman-Parker J, Cayre Y, Douay L

机构信息

Service d'Hématologie Biologique, Hĵpital d'enfants Armand Trousseau, Paris, France.

出版信息

Leuk Lymphoma. 2001 Aug;42(4):675-82. doi: 10.3109/10428190109099329.

DOI:10.3109/10428190109099329
PMID:11697497
Abstract

Prospective clinical studies including large numbers of patients have led to the conclusion that co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia (My+ ALL) does not have prognostic significance. However, reports of the frequency of My+ ALL in children vary widely across laboratories using different mAb clones and staining and analysing procedures. Taking two commonly accepted thresholds of positivity for myeloid antigens (20 and 30%), we analysed the immunoreactivity of the most widely employed mAb clones against CD13 (SJ1D1, L138 and My7) and CD33 (My9, P67.6 and D3HL60) and compared the proportions of My+ ALL detected by these clones in childhood ALL. The correlation between myeloid antigen expression and the presence of the t(12;21) translocation was analysed concomitantly in the same samples. The percentage of ALL cases positive for myeloid markers varied significantly depending on the mAb clone and the positive threshold. Among patients with B-ALL, the proportion of CD13+ ALL was significantly lower using SJ1D1 than using L138 or My7, while the proportion of CD33+ ALL was significantly higher for My9 than for P67.6 or D3HL60. Analysis of the co-expression of CD13 and CD33 on B-ALL cells using combinations of mAb clones showed that this frequency was either underestimated by the SJ1D1/D3HL60 or overestimated by the L138/P67.6 and My7/My9 combinations. A correlation between CD13/CD33 positivity and the t(12;21) translocation was uniformly observed in B-ALL patients for a positive threshold of 30%, whereas SJ1D1/D3HL60 detected no correlation between t(12;21) and CD13/CD33 positivity when the threshold was lowered to 20%. These data show that the mAb clones commonly used to detect the CD13 and CD33 surface antigens have variable immunoreactivity against childhood ALL cells, which may partly explain the conflicting reports concerning the prognostic significance of myeloid antigen expression in paediatric ALL and its association with different translocations. The present findings may also be of clinical importance for therapeutic choices.

摘要

包括大量患者的前瞻性临床研究得出结论,儿童急性淋巴细胞白血病(My⁺ ALL)中髓系抗原的共表达不具有预后意义。然而,使用不同单克隆抗体(mAb)克隆以及染色和分析程序的各实验室报告的儿童My⁺ ALL发生率差异很大。采用两个普遍认可的髓系抗原阳性阈值(20%和30%),我们分析了针对CD13(SJ1D1、L138和My7)和CD33(My9、P67.6和D3HL60)的最广泛使用的mAb克隆的免疫反应性,并比较了这些克隆在儿童ALL中检测到的My⁺ ALL比例。在相同样本中同时分析了髓系抗原表达与t(12;21)易位存在之间的相关性。髓系标志物阳性的ALL病例百分比因mAb克隆和阳性阈值的不同而有显著差异。在B-ALL患者中,使用SJ1D1检测到的CD13⁺ ALL比例显著低于使用L138或My7时的比例,而使用My9检测到的CD33⁺ ALL比例显著高于使用P67.6或D3HL60时的比例。使用mAb克隆组合分析B-ALL细胞上CD13和CD33的共表达情况表明,SJ1D1/D3HL60组合会低估这一频率,而L138/P67.6和My7/My9组合会高估这一频率。在B-ALL患者中,当阳性阈值为30%时,一致观察到CD13/CD33阳性与t(12;21)易位之间存在相关性,而当阈值降至20%时,SJ1D1/D3HL60未检测到t(12;21)与CD13/CD33阳性之间的相关性。这些数据表明,常用于检测CD13和CD33表面抗原的mAb克隆对儿童ALL细胞具有可变的免疫反应性,这可能部分解释了关于髓系抗原表达在儿童ALL中的预后意义及其与不同易位的关联的相互矛盾的报告。目前的研究结果对于治疗选择也可能具有临床重要性。

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