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Neonates with Down's syndrome occasionally show an excess of blasts in their peripheral blood. This disorder spontaneously resolves within several months and is called transient abnormal myelopoiesis (TAM) or transient myeloproliferative disorder. It has been uncertain whether the excess of blasts in TAM is a result of a clonal proliferation or a polyclonal reactive condition. The clonality of cells in females can be examined by analysis of the methylation patterns of the X chromosomes of proliferating cells using restriction fragment length polymorphism (RFLP). Using this strategy, we studied three females with Down's syndrome accompanied by TAM who showed heterozygosity in RFLP of either the hypoxanthine phosphoribosyltransferase or phosphoglycerate kinase gene. Analysis of the methylation patterns of these genes demonstrated a clonal nature for blasts in three patients. Thus, TAM is a clonal proliferative disorder. In addition, lymphocytes with a normal appearance contained in analyzed samples from these patients also showed a monoclonal pattern, suggesting that TAM may be a disorder of multipotent stem cells.
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