Clonality analysis of refractory anemia with ring sideroblasts: simultaneous study of clonality and cytochemistry of...

X chromosome inactivation and polymorphism of the human androgen receptor (HUMARA) gene has been applied for analyzing the clonality of blood cells. In the present study, the clonal relationship was investigated between peripheral blood polymorphonuclear cells (PMNCs) and marrow progenitor cells and the origin of ringed sideroblasts in patients with refractory anemia with ring sideroblasts (RARS) by polymerase chain reaction (PCR) of HUMARA gene. The X-inactivation patterns of circulating PMNCs and T lymphocytes as well as individual granulocyte colonies grown in vitro from bone marrow cells were analyzed. The development of ringed sideroblasts in erythroid colonies by iron staining and their X-inactivation pattern were also examined. All three RARS patients showed monoclonal PMNCs. In granulocyte colonies, however, two different X-inactivation patterns were observed in all patients, indicating that non-clonal progenitor cells remained in the bone marrow. All erythroid colonies consisted of ringed sideroblasts exclusively showed one pattern dominant in those of PMNCs. Our findings suggest that non-clonal progenitor cells persist in some RARS cases, that erythroid progenitors show mosaicism, and that ringed sideroblasts may be derived from an abnormal clone involved in the pathogenesis of this disease.