Macedo A, Orfão A, Vidriales M B, López-Berges M C, Valverde B, González M, Caballero M D, Ramos F, Martínez M, Fernández-Calvo J
Servicio de Hematología, Hospital Universitario, Salamanca, Spain.
Ann Hematol. 1995 Apr;70(4):189-94. doi: 10.1007/BF01700374.
The existence of leukemic-associated phenotypes has been suggested to be a valuable tool for the detection of minimal residual disease (MRD) in AML patients, as they would allow to distinguish leukemic blast cells from normal hematopoietic progenitors. The present study was designed to analyze in which proportion of AML patients the immunological detection of MRD is feasible, based on the presence of aberrant phenotypes that allow the distinction of leukemic from normal cells. For this purpose we have prospectively investigated the blast cells from 40 AML patients at diagnosis with a large panel of MoAb in double and triple staining combinations analyzed at flow cytometry, in order to detect aberrant phenotypes on blast cells (lineage infidelity, antigenic overexpression, and asynchronous antigenic expression, as well as aberrant light-scatter pattern). In the analysis of the 40 AML cases more than one blast cell subset, distinguished by its different antigenic expression, was detected in 85% of the patients: five different phenotypic blast cell subsets were observed in six cases, four in 13 patients, three subsets in three cases, and two in 12 patients; only six cases showed a homogeneous phenotypical blast cell population. Twenty-nine of the 40 AML cases analyzed (73%) showed the existence of at least one aberrant phenotype: in 15 cases the myeloid blast cells co-expressed lymphoid-associated antigens (CD2, CD5, CD7, and/or CD19)--lineage infidelity--; asynchronous antigen expression was detected in 25 patients (CD34+CD56+, CD34+CD11b+, CD34+CD14+, CD117+CD15+, CD33-CD13+, CD13-CD15+, HLADR + CD15 , HLADR-CD14+CD11b+ CD4+); seven cases displayed antigen overexpression (CD13, CD33, CD15, or CD14); and in 13 patients leukemic cells had an abnormal FSC/SSC distribution according to their phenotype. These results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients.
白血病相关表型的存在被认为是检测急性髓系白血病（AML）患者微小残留病（MRD）的一种有价值的工具，因为它们能够区分白血病原始细胞与正常造血祖细胞。本研究旨在基于能够区分白血病细胞与正常细胞的异常表型的存在情况，分析在多大比例的AML患者中进行MRD的免疫学检测是可行的。为此，我们前瞻性地研究了40例AML患者诊断时的原始细胞，使用大量单克隆抗体（MoAb）进行双色和三色染色组合，并通过流式细胞术进行分析，以检测原始细胞上的异常表型（谱系不忠实、抗原过度表达、异步抗原表达以及异常光散射模式）。在对40例AML病例的分析中，85%的患者检测到不止一个以不同抗原表达区分的原始细胞亚群：6例患者观察到5种不同表型的原始细胞亚群，13例患者为4种，3例患者为3种亚群，12例患者为2种；只有6例显示出均匀的表型原始细胞群体。在分析的40例AML病例中，有29例（73%）显示存在至少一种异常表型：15例中髓系原始细胞共表达淋巴系相关抗原（CD2、CD5、CD7和/或CD19）——谱系不忠实；25例患者检测到异步抗原表达（CD34+CD56+、CD34+CD11b+、CD34+CD14+、CD117+CD15+、CD33-CD13+、CD13-CD15+、HLADR + CD15 、HLADR-CD14+CD11b+ CD4+）；7例显示抗原过度表达（CD13、CD33、CD15或CD14）；13例患者的白血病细胞根据其表型具有异常的前向散射光/侧向散射光（FSC/SSC）分布。这些结果表明，基于异常表型存在情况的MRD免疫学检测方法可用于大多数AML患者。
