Independent clones at separable stages of differentiation, bearing different GATA1 mutations in the same TMD patient with Down Syndrome

Somatic mutations of the megakaryocytic and erythroid differentiation factor GATA1 in transient myeloproliferative disorder (TMD) of Down syndrome (DS) occur in utero,1-5 and are detectable in fetal liver.1 Multiple GATA1 mutations can occur in the same DS-TMD patient.5 The exact cell type and developmental time-frame in which these mutations occur have not yet been identified. If the acquisition of such mutations occurs within a very limited time frame at a specific stage of differentiation, one would expect individual clones from a case of DS-TMD with multiple independent clones to be arrested at a similar stage of differentiation. We present data which argue against this hypothesis, and demonstrate for the first time that multiple independent GATA1 mutations in the same individual can be found in clones physically separable from each other by surface maturation markers