Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome.
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.
Division of Hematology, University of Pavia Medical School, IRCCS Policlinico S. Matteo, Pavia, Italy.
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MG
Della Porta
L
L
Malcovati
R
R
Invernizzi
E
E
Travaglino
C
C
Pascutto
M
M
Maffioli
A
A
Gallì
S
S
Boggi
D
D
Pietra
L
L
Vanelli
C
C
Marseglia
S
S
Levi
P
P
Arosio
M
M
Lazzarino
M
M
Cazzola
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000378:metabolism; D001052:Apoferritins; D001854:Bone Marrow Cells / Q000473:pathology; D015331:Cohort Studies; D020732:Cytogenetic Analysis / Q000379:methods; D000071063:Endoglin; D041905:Erythroid Cells / Q000378:metabolism / Q000473:pathology*; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005293:Ferritins / Q000096:biosynthesis; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000737:chemistry; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018952:Antigens, CD34; C068126:CD71 antigen; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D005293:Ferritins; D001052:Apoferritins