title: Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs significantly from other diseases with morphologically identical or similar blasts.
abstract: OBJECTIVE
  Children with Down Syndrome (DS) have a 20-40 fold increased risk of developing acute myeloid leukemia (AML), mainly of the megakaryoblastic subtype (AMKL). Approximately 10 % of newborns with DS show transient myeloproliferative disease (TMD) which normally resolves spontaneously. The blast cells of both entities show megakaryoblastic/erythroblastic features (M7/M6) and cannot be distinguished by morphological characteristics.
  
  
  METHODS
  Blast cells of 62 children were analyzed by four-color flow cytometry and dual color fluorescence microscopy.
  
  
  RESULTS
  The immunophenotype of blast cells from children with TMD and DS-AMKL is characterized by the expression of CD33 (+)/CD13 (+/-)/CD38 (+)/CD117 (+)/CD34 (+/-)/CD7 (+)/CD56 (+/-)/CD36 (+)/CD71 (+)/CD42b (+)/CD4dim (+)/TPO-R (+)/EPO-R (-)/IL-3-Ralpha (+)/IL-6-Ralpha (-). Non-DS children with morphologically related diseases, i. e. myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML), or AML-M6 and AML-M7, did not show this expression profile. CD34 expression was observed in 93 % of TMD, but only 50 % of DS-AMKL patients. The blast cells of all TMD and DS-AMKL cases were positive for TPO-R and IL-3R, whereas EPO-R and IL-6R were absent.
  
  
  CONCLUSIONS
  Immunophenotyping by the use of surface antigens and growth factor receptors is a useful tool to discriminate TMD and DS-AMKL from diseases with morphologically similar or identical blasts. The absence of EPO-R on the blast cells might be a sign of the high expression of the mutated -- and less active -- GATA1 in DS. The higher amount of CD34 co-expression in TMD may be interpreted to indicate that TMD is a slightly more immature disease than DS-AMKL.
authors.affiliation: University Children's Hospital Muenster, Department of Pediatric Hematology and Oncology, 48129 Muenster. langebra@uni-muenster.de
authors.forename: C
authors.initials: C
authors.lastname: Langebrake
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.forename: D
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D003937:Diagnosis, Differential; D004314:Down Syndrome / Q000150:complications* / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000175:diagnosis / Q000276:immunology; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000276:immunology*; D008856:Microscopy, Fluorescence / Q000379:methods; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000276:immunology*; D012680:Sensitivity and Specificity; D013997:Time Factors