Evidence for nonclonal hematopoietic progenitor cell populations in bone marrow of patients with myelodysplastic syndromes

Abstract

Clonality of marrow hematopoietic progenitor cells in myelodysplastic syndromes (MDS) was analyzed by X-chromosome inactivation pattern using polymerase chain reaction (PCR). Five female patients were included in this study; two with refractory anemia (RA) and three with RA with excess blasts (RAEB). They were heterozygous for BstXI restriction fragment length polymorphisms (RFLP) of the X-chromosome-linked phosphoglycerate kinase (PGK) gene. In each patient, erythroid and nonerythroid colonies, grown in the presence of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibited no remarkable difference in clonal constitution. Two patients showed only one methylation pattern, suggesting the monoclonal origin of hematopoietic progenitor cells. Colonies of two other patients exhibited predominant and minor methylation patterns in PGK gene, indicating that nonclonal progenitor cells remain a minor population. The bone marrow of one patient appeared to contain a greater proportion of nonclonal progenitors. Stem cell factor (SCF), a potent colony- stimulating factor, enhanced both erythroid and nonerythroid colony formation. However, it did not notably alter the clonal constitutions. We conclude that nonclonal hematopoietic progenitor cells can persist in a substantial number of MDS patients.

Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients

“…The rate of administration may play a critical role in erythroid response, and a continuous humoral stimulus on erythroid progenitors in MDS may be necessary to elicit the biological response to rHuEpo, as a post‐translational defect in the Epo response pathway has been demonstrated in MDS, resulting in the suppression of both the Epo‐dependent proliferation and the differentiation induction by Epo (Hoefsloot et al , 1997; Fontenay‐Roupie et al , 1999). The co‐existence of normal haematopoietic progenitors with abnormal ones (Asano et al , 1994) and the presence of certain abnormalities in erythroid progenitors that need higher concentrations of Epo to respond in vitro (Aoki & Shibata, 1992) may suggest that the prolonged administration of rHuEpo enhances stimulation of erythroid progenitors and produces a response to treatment.…”

Favourable response to antithymocyte or antilymphocyte globulin in low‐risk myelodysplastic syndrome patients with a ‘non‐clonal’ pattern of X‐chromosome inactivation in bone marrow cells

“…However, we found that the response to ATG/ALG appears to be related to a ‘non‐clonal’ pattern of bone marrow cells on X‐chromosome inactivation analysis. A detailed review of the pertinent literature revealed a total of 26 ‘polyclonal MDS’ (2, 5–13, 25). Mainly, there are three possible reasons for ‘non‐clonal’ XCIP in patients with MDS.…”

“…However, there have also been a few MDS patients with peripheral blood (PB) or bone marrow (BM) cells showing polyclonal X‐chromosome inactivation patterns (XCIP). This observation was attributed to persistence of a considerable amount of normal hematopoiesis (2, 5–13).…”

Quantitative, phenotypic, and functional evaluation of basophils in myelodysplastic syndromes

“…Myeloid blood cells in MDS, including basophils and eosinophils, may belong to the malignant clone or may represent a mixture of clonal and nonclonal cells [34–36]. Whether the basophils examined in our MDS patients belonged to the malignant clone or not, remains unknown.…”