Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome

Leukemia. 2006 Apr;20(4):549-55. doi: 10.1038/sj.leu.2404142.

Abstract

Erythroid dysplasia is the pathologic hallmark of myelodysplastic syndromes (MDS). To develop a quantitative flow-cytometry approach to its evaluation, we analyzed the expression of CD71, CD105, cytosolic H-ferritin (HF), cytosolic L-ferritin (LF) and mitochondrial ferritin (MtF) in erythroblasts from 104 MDS patients, 69 pathologic control patients and 19 healthy subjects. Six-parameter, 4-color flow cytometry was employed, and data were expressed as mean fluorescence intensity. Compared with pathologic and healthy controls, MDS patients had higher expression of HF (P < 0.001) and CD105 (P < 0.001), and lower expression of CD71 (P < 0.001). MtF was specifically detected in MDS with ringed sideroblasts, and there was a close relationship between its expression and Prussian blue staining (r = 0.89, P < 0.001). In vitro cultures of myelodysplastic hematopoietic progenitors showed that both HF and MtF were expressed at a very early stage of erythroid differentiation, and that MtF expression is specifically related to mitochondrial iron loading. A classification function based on expression levels of HF, CD71 and CD105 allowed us to correctly classify > 95% of MDS patients. This flow-cytometry approach provides an accurate quantitative evaluation of erythroid dysplasia and allows a reliable diagnosis of sideroblastic anemia, and may therefore be a useful tool in the work-up of patients with MDS.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / biosynthesis
  • Antigens, CD34 / metabolism
  • Apoferritins
  • Bone Marrow Cells / pathology
  • Cohort Studies
  • Cytogenetic Analysis / methods
  • Endoglin
  • Erythroid Cells / metabolism
  • Erythroid Cells / pathology*
  • Erythroid Precursor Cells / metabolism
  • Erythroid Precursor Cells / pathology
  • Female
  • Ferritins / biosynthesis
  • Flow Cytometry / methods*
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Mitochondria / chemistry
  • Myelodysplastic Syndromes / classification
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology*
  • Prospective Studies
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Transferrin / biosynthesis
  • Sensitivity and Specificity
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Antigens, CD34
  • CD71 antigen
  • ENG protein, human
  • Endoglin
  • Receptors, Cell Surface
  • Receptors, Transferrin
  • Ferritins
  • Apoferritins