Langebrake Claudia, Brinkmann Iris, Teigler-Schlegel Andrea, Creutzig Ursula, Griesinger Frank, Puhlmann Ulrike, Reinhardt Dirk
Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany.
Cytometry B Clin Cytom. 2005 Jan;63(1):1-9. doi: 10.1002/cyto.b.20037.
Determination of antigen expression patterns is, in addition to morphologic analysis, essential to the diagnosis of acute myeloid leukemia (AML). The present study was performed to determine (a) the degree of changes in immunophenotype and their consequences on the monitoring of minimal residual disease (MRD) in childhood AML and (b) whether certain clusters of changes in antigen expression patterns exist between diagnosis and relapse.
Bone marrow specimens of 48 children enrolled in the German AML-BFM-93/98 (Acute Myeloid Leukemia-Berlin-Frankfurt-Munster) studies were analyzed immunologically, morphologically, and genetically at diagnosis and at first relapse.
The immunophenotypes by flow cytometry differed by at least one antigen between samples at presentation and relapse in 42 of 48 children (88%). More children displayed an immature phenotype at relapse (43 of 47, 91.5%, vs. 37 of 48, 77%; P = 0.05) with expression of CD34 and/or CD117. This was reflected by a gain of markers that are associated with lineage immaturity in 18 of 25 (72%) of cases, whereas the loss of such antigens was observed in 6 of 25 (24%) patients. We did not observe significant changes for lineage specific markers, with comparable occurrences of loss or gain of myeloid and lymphoid antigens in the sample pairs. Only minimal changes were seen for morphologic and genetic features.
An antigenic shift was observed in 88% of cases in this study. The antibody panels used for MRD monitoring in childhood AML should therefore not be restricted to the immunophenotype detected at presentation but should include in particular markers of lineage immaturity. The clinical observation of a shift toward a more immature phenotype of the myeloblasts is consistent with the model of a clonal evolution of a leukemic stem cell.
除形态学分析外，抗原表达模式的测定对于急性髓系白血病（AML）的诊断至关重要。本研究旨在确定：（a）儿童AML免疫表型的变化程度及其对微小残留病（MRD）监测的影响；（b）诊断与复发之间是否存在特定的抗原表达模式变化簇。
对参加德国AML-BFM-93/98（急性髓系白血病-柏林-法兰克福-明斯特）研究的48例儿童的骨髓标本在诊断时和首次复发时进行免疫、形态和基因分析。
48例儿童中，42例（88%）在初诊和复发时样本的流式细胞术免疫表型至少有1种抗原不同。更多儿童在复发时表现为不成熟表型（47例中的43例，91.5%，对比48例中的37例，77%；P = 0.05），伴有CD34和/或CD117表达。这表现为25例中的18例（72%）出现与谱系不成熟相关标志物增加，而25例中的6例（24%）患者出现此类抗原丢失。我们未观察到谱系特异性标志物有显著变化，样本对中髓系和淋巴系抗原丢失或增加的发生率相当。形态和基因特征仅见微小变化。
本研究中88%的病例观察到抗原转变。因此，用于儿童AML中MRD监测的抗体组合不应局限于初诊时检测到的免疫表型，尤其应包括谱系不成熟的标志物。髓母细胞向更不成熟表型转变的临床观察与白血病干细胞克隆进化模型一致。
