Departments of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
BMC Cancer. 2013 Mar 8;13:107. doi: 10.1186/1471-2407-13-107.
The prognostic implication of immunophenotyping in acute myeloid leukemia (AML) patients with NPM1 mutation remains unclear.
Ninety-four of 543 AML patients diagnosed with NPM1 mutation between 1987 and 2007 were studied. The expression of surface antigens on leukemic cells was evaluated with respect to clinical manifestations and outcomes. In order to validate the prognostic effect of the immunophenotypic cluster, another 36 patients with NPM1 mutation diagnosed between 2008 and 2010 were analyzed.
Ninety-four patients with NPM1 mutations and complete immunophenotyping data were enrolled for a hierarchical cluster analysis and the result was correlated with clinico-laboratory characteristics. Clustering analysis divided the patients with NPM1 mutations into the following two groups: group I, CD34(-)/CD7(-), but with variable expression of HLA-DR; and group II, HLA DR(+)/CD34(+)/CD7(+). With a median follow-up of 53 months, the group II patients had a significantly shorter relapse-free survival (RFS, median: 3 vs. 23 months, p = 0.006) and overall survival (OS, median: 11 vs. 40 months, p = 0.02) than group I patients. Multivariate analysis of variables, including clinico-laboratory data and other gene mutations revealed that the immunophenotypic cluster is an independent prognostic factor (RFS, p = 0.002; OS, p = 0.024). In order to confirm the prognostic effect of the immunophenotypic cluster, another 36 patients with NPM1 mutation diagnosed between 2008 and 2010 were validated. Hierarchical cluster analysis also showed two distinct clusters, group I patient showed significant better RFS (p = 0.021), and OS (p = 0.055). In total, we stratified 130 NPM1-mutant patients, by FLT3-ITD mutation and immunophenotypic cluster into distinct prognostic groups (RFS, p < 0.001 and OS, p = 0.017).
Among NPM1-mutated AML, the antigen expression pattern of HLADR(+) CD34(+) CD7(+) is associated with a poor prognosis, independent to the FLT3-ITD mutation.
NPM1 突变的急性髓系白血病（AML）患者免疫表型的预后意义仍不清楚。
研究了 1987 年至 2007 年间诊断为 NPM1 突变的 543 例 AML 患者中的 94 例。评估了白血病细胞表面抗原的表达与临床表现和结局的关系。为了验证免疫表型聚类的预后效应，还分析了 2008 年至 2010 年间诊断的另外 36 例 NPM1 突变患者。
纳入了 94 例 NPM1 突变且具有完整免疫表型数据的患者进行层次聚类分析，并将结果与临床实验室特征相关联。聚类分析将 NPM1 突变患者分为以下两组：组 I，CD34（-）/CD7（-），但 HLA-DR 表达可变；组 II，HLA-DR（+）/CD34（+）/CD7（+）。中位随访 53 个月后，组 II 患者的无复发生存期（RFS，中位：3 个月 vs. 23 个月，p=0.006）和总生存期（OS，中位：11 个月 vs. 40 个月，p=0.02）明显短于组 I 患者。对包括临床实验室数据和其他基因突变在内的变量进行多变量分析表明，免疫表型聚类是独立的预后因素（RFS，p=0.002；OS，p=0.024）。为了验证免疫表型聚类的预后效应，还验证了 2008 年至 2010 年间诊断的另外 36 例 NPM1 突变患者。层次聚类分析也显示出两组截然不同的患者，组 I 患者的 RFS（p=0.021）和 OS（p=0.055）显著更好。总的来说，我们根据 FLT3-ITD 突变和免疫表型聚类将 130 例 NPM1 突变患者分为不同的预后组（RFS，p<0.001；OS，p=0.017）。
在 NPM1 突变的 AML 中，HLA-DR（+）CD34（+）CD7（+）的抗原表达模式与预后不良相关，与 FLT3-ITD 突变无关。
