Iron is essential for cell proliferation,
heme synthesis, and a variety of cellular metabolic processes. In most cells,
transferrin receptor-mediated endocytosis is a major pathway for cellular
iron uptake. Recently,
transferrin receptor 2 (TfR2), another receptor for
transferrin, was cloned. High levels of expression of TfR2
messenger RNA (
mRNA) occur in the liver, as well as in HepG2 (a
hepatoma cell line) and K562 (an erythroid
leukemia cell line). In this study, TfR2
mRNA expression was analyzed in hematological cell lines, normal erythroid cells at various stages of differentiation, and
leukemia and
preleukemia cells. High levels of TfR2 expression occurred in all of the erythroid cell lines that were examined. Erythroid-specific expression of TfR2
protein in bone marrow cells was confirmed by immunohistochemical staining. Expression of TfR2
mRNA was high in normal CD34(+) erythroid precursor cells, and levels decreased during erythroid differentiation in vitro. Levels of expression of TfR2-alpha
mRNA were significantly higher in
erythroleukemia (M6) marrow samples than in nonmalignant control marrow samples. In addition, relatively higher levels of TfR2-alpha
mRNA expression occurred in some samples of
myelodysplastic syndrome that had erythroid
hyperplasia in bone marrow,
acute myelogenous leukemia M1, M2, and
chronic myelogenous leukemia. Expression profiles of normal members of the erythroid lineage suggest that TfR2-alpha may be a useful marker of early erythroid precursor cells. The clinical significance of TfR2-alpha expression in
leukemia cells remains to be determined.