Schneider Tanja, Flörcken Anne, Singh Anju, Türkmen Seval, Burmeister Thomas, Anagnostopoulos Ioannis, Pezzutto Antonio, Dörken Bernd, Westermann Jörg
Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow-Klinikum, Berlin, Germany.
Ann Hematol. 2015 Aug;94(8):1337-45. doi: 10.1007/s00277-015-2400-5. Epub 2015 May 22.
The European LeukemiaNet (ELN) classification is widely accepted for risk stratification of patients with acute myeloid leukemia (AML). In order to establish immunophenotypic features that predict prognosis, the expression of single AML blast cell antigens has been evaluated with partly conflicting results; however, the influence of immunophenotypic blast maturity is largely unknown. In our study, 300 AML patients diagnosed at our institution between January 2003 and April 2012 were analyzed. A flow cytometric maturity score was developed in order to distinguish "mature" AML (AML-ma) from "immature" AML (AML-im) by quantitative expression levels of early progenitor cell antigens (CD34, CD117, and TdT). AML-ma showed significantly longer relapse-free survival (RFS) and overall survival (OS) than AML-im (p < 0.001). Interestingly, statistically significant differences in RFS and OS were maintained within the "intermediate-risk" group according to ELN (RFS, 7.0 years (AML-ma) vs. 3.3 years (AML-im); p = 0.002; OS, 5.1 years (AML-ma) vs. 3.0 years (AML-im); p = 0.022). Our novel flow cytometric score easily determines AML blast maturity and can predict clinical outcome. It remains to be clarified whether these results simply reflect an accumulation of favorable molecular phenotypes in the AML-ma subgroup or whether they rely on biological differences such as a higher proportion of leukemia stem cells and/or a higher degree of genetic instability within the AML-im subgroup.
欧洲白血病网(ELN)分类法在急性髓系白血病(AML)患者的风险分层中被广泛接受。为了确定预测预后的免疫表型特征,已对单个AML原始细胞抗原的表达进行了评估,结果部分相互矛盾;然而,免疫表型原始细胞成熟度的影响在很大程度上尚不清楚。在我们的研究中,分析了2003年1月至2012年4月在我们机构诊断的300例AML患者。通过早期祖细胞抗原(CD34、CD117和TdT)的定量表达水平,制定了流式细胞术成熟度评分,以区分“成熟”AML(AML-ma)和“不成熟”AML(AML-im)。AML-ma的无复发生存期(RFS)和总生存期(OS)明显长于AML-im(p<0.001)。有趣的是,根据ELN分类,“中危”组内RFS和OS的差异具有统计学意义(RFS,7.0年(AML-ma)对3.3年(AML-im);p=0.002;OS,5.1年(AML-ma)对3.0年(AML-im);p=0.022)。我们新的流式细胞术评分能够轻松确定AML原始细胞的成熟度,并可预测临床结果。这些结果究竟是仅仅反映了AML-ma亚组中有利分子表型的积累,还是依赖于生物学差异,如AML-im亚组中白血病干细胞比例较高和/或遗传不稳定性程度较高,仍有待阐明。