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

Background:Loss of HLADR and CD34 is a wellknown 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 HLADRnegacute myeloid leukemia patients would allow more clearly define criteria to separate APL from nonAPL 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 HLADRnegnonAPL patients were identified. The main differential characteristics of HLADRnegnonAPL included high CXCR4 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 cuplike 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 HLADRnegnonAPL patients. Even in the CD34possubgroup of HLADRnegnonAPL 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 HLADRnegleukemia subgroups is possible indicating that both groups are biologically distinct. © 2009 Clinical Cytometry Society