Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs significantly from other diseases with morphologically identical or similar blasts

Background and objectives: 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. Design and methods: Blast cells of 62 children were analyzed by four-color flow cytometry and dual color fluorescence microscopy. Results: The immunopheno-type of blast cells from children with TMD and DS-AMKL is characterized by the expression of CD33(+)/CD13(+/-) /CD38(+)/CD117(+)/CD341(+/-)/CD7(+)/CD56(+/-) /CD36(+)/CD71(+)/CD42b(+)/CD4dim(+)/TPO-R+/EPO-R-/IL-3-R alpha(+)/IL- 6-R alpha(-). 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.