HLA‐DRneg patients without acute promyelocytic leukemia show distinct immunophenotypic, genetic, molecular, and cytomorphologic characteristics compared to acute promyelocytic leukemia

Abstract

Background: Loss of HLA‐DR and CD34 is a well‐known characteristic of malignant promyelocytes in acute promyelocytic leukemia (APL). However, this immunophenotype is not specific for APL. The purpose of this study was to investigate whether further biological characterization of the HLA‐DR^neg acute myeloid leukemia patients would allow more clearly define criteria to separate APL from non‐APL patients. Methods: Immunophenotyping, cytogenetics, molecular analyses, and cytomorphology were prospectively performed within routine leukemia diagnostics of 800 patients included in different prospective acute myeloid leukemia multicenter trials. Results: Beside 60 APL, an additional 62 HLA‐DR^neg non‐APL patients were identified. The main differential characteristics of HLA‐DR^neg non‐APL included high CXCR‐4 expression in most patients and almost all leukemia cells, a significantly higher proportion of patients presenting with NPM1 mutations as well as the significant association with cup‐like nuclear morphology. The biological distinctness of both leukemia subtypes was further emphasized by the complete absence of aberrant CD2 expression and increased leukocyte and platelet counts in HLA‐DR^neg non‐APL patients. Even in the CD34^pos subgroup of HLA‐DR^neg non‐APL all those features contributed in at least the same way to the separation from APL. Conclusions: The results of the present study show that an immunophenotypic, molecular, and cytomorphologic separation of both HLA‐DR^neg leukemia subgroups is possible indicating that both groups are biologically distinct. © 2009 Clinical Cytometry Society