Background And Objectives: Clonal hematopoiesis is the hallmark of myelodysplastic syndromes, but the role played by pluripotent stem cells and progenitor cells in these disorders remains unclear.
Design And Methods: Eight female patients with myelodysplastic syndrome were studied. X-chromosome inactivation patterns were analyzed in peripheral blood granulocytes, T-lymphocytes, single colonies originating from bone marrow progenitors and pluripotent stem cells, using the human androgen receptor locus polymorphism assay.
Results: Granulocytes and progenitor cells were monoclonal in 7/8 cases. Immature stem cells showed a non-clonal pattern of X-inactivation and were detectable at diagnosis in the presence of clonal hematopoiesis. T-lymphocyte clonality was heterogeneous.
Interpretation And Conclusions: In myelodysplastic syndromes, hematopoiesis may be dominated by a neoplastic clone by virtue of its biological advantage over a residual polyclonal, probably still normal, population of immature stem cells still able to grow in vitro.
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