title: Immunophenotypic differences between diagnosis and relapse in childhood AML: Implications for MRD monitoring.
abstract: BACKGROUND
  Determination of antigen expression patterns is, in addition to morphologic analysis, essential to the diagnosis of acute myeloid leukemia (AML). The present study was performed to determine (a) the degree of changes in immunophenotype and their consequences on the monitoring of minimal residual disease (MRD) in childhood AML and (b) whether certain clusters of changes in antigen expression patterns exist between diagnosis and relapse.
  
  
  METHODS
  Bone marrow specimens of 48 children enrolled in the German AML-BFM-93/98 (Acute Myeloid Leukemia-Berlin-Frankfurt-Munster) studies were analyzed immunologically, morphologically, and genetically at diagnosis and at first relapse.
  
  
  RESULTS
  The immunophenotypes by flow cytometry differed by at least one antigen between samples at presentation and relapse in 42 of 48 children (88%). More children displayed an immature phenotype at relapse (43 of 47, 91.5%, vs. 37 of 48, 77%; P = 0.05) with expression of CD34 and/or CD117. This was reflected by a gain of markers that are associated with lineage immaturity in 18 of 25 (72%) of cases, whereas the loss of such antigens was observed in 6 of 25 (24%) patients. We did not observe significant changes for lineage specific markers, with comparable occurrences of loss or gain of myeloid and lymphoid antigens in the sample pairs. Only minimal changes were seen for morphologic and genetic features.
  
  
  CONCLUSIONS
  An antigenic shift was observed in 88% of cases in this study. The antibody panels used for MRD monitoring in childhood AML should therefore not be restricted to the immunophenotype detected at presentation but should include in particular markers of lineage immaturity. The clinical observation of a shift toward a more immature phenotype of the myeloblasts is consistent with the model of a clonal evolution of a leukemic stem cell.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany. langebra@uni-muenster.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Langebrake
authors.forename: Iris
authors.initials: I
authors.lastname: Brinkmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Teigler-Schlegel
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Frank
authors.initials: F
authors.lastname: Griesinger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Puhlmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D007223:Infant; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000276:immunology; D012008:Recurrence
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor