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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2714-2719
HEMATOPOIESIS
Expression of transferrin receptor 2 in normal and neoplastic
hematopoietic cells
Hiroshi Kawabata,
Tsuyoshi Nakamaki,
Pranvera Ikonomi,
Reginald D. Smith,
Rasha S. Germain, and
H. Phillip Koeffler
From the Division of Hematology/Oncology, Department of
Medicine, Cedars-Sinai Medical Center, Burns and Allen Research
Institute, University of California, Los Angeles, School of Medicine;
the Department of Hematology, Showa University School of Medicine,
Tokyo, Japan; the Division of Hematology/Immunology, Kanazawa Medical
University, Uchinada, Japan; and the Laboratory of Chemical Biology,
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD.
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- mRNA were significantly higher in
erythroleukemia (M6) marrow samples than in nonmalignant control marrow
samples. In addition, relatively higher levels of TfR2-
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- may be
a useful marker of early erythroid precursor cells. The clinical
significance of TfR2- expression in leukemia cells
remains to be determined.
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