Abstract
BackgroundThe prognostic implication of immunophenotyping in acute myeloid leukemia (AML) patients with NPM1 mutation remains unclear.MethodsNinety-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.ResultsNinety-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).ConclusionsAmong NPM1-mutated AML, the antigen expression pattern of HLADR(+) CD34(+) CD7(+) is associated with a poor prognosis, independent to the FLT3-ITD mutation.
Highlights
The prognostic implication of immunophenotyping in acute myeloid leukemia (AML) patients with NPM1 mutation remains unclear
NPM1 mutations are usually associated with absence of HLA-DR and CD34 expression [11]; the surface marker expression in blasts varies in individual AML patients and the clinical implication of immunophenotype in this subtype of AML remains unclear
In order to confirm the prognostic implication of the immunophenotypic profile, another 36 AML patients diagnosed with NPM1 mutation between 2008 and 2010 were enrolled as the validation cohort
Summary
The prognostic implication of immunophenotyping in acute myeloid leukemia (AML) patients with NPM1 mutation remains unclear. NPM1 mutations are usually associated with absence of HLA-DR and CD34 expression [11]; the surface marker expression in blasts varies in individual AML patients and the clinical implication of immunophenotype in this subtype of AML remains unclear. Previous reports have suggested that expression of some surface antigens is correlated with clinical outcome in AML patients [12,13,14], but the prognostic significance of immunophenotype is still an issue of controversy [15,16]. Most studies analyzed the prognostic implication of individual antigens, and usually in a heterogeneous population of AML patients with various genetic abnormalities. We performed a hierarchical cluster analysis of the immunophenotype expression profiles in a relatively homogeneous cohort of AML patients with NPM1 mutations, and correlated the results with clinical characteristics, other gene mutations, and prognoses
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