Primitive hematopoietic stem cells show a polyclonal pattern in myelodysplastic syndromes

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.