Mechanisms of differential transferrin receptor expression in normal hematopoiesis

Sposi, Nadia Maria; Cianetti, L; Tritarelli, Elena; Pelosi, Elvira; Militi, Stefania; Barberi, Tiziano; Gabbianelli, Marco; Saulle, Ernestina; Kühn, Lukas C.; Peschle, Cesare; Testa, Ugo

doi:10.1046/j.1432-1033.2000.01769.x

Cited by 42 publications

(38 citation statements)

References 65 publications

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“…This hyper-up-regulation of CD71/ TfR in early precursors (R1 to R2) is completely Epo-dependent, 16 and mediated via TfR gene transcriptional and posttranscriptional mechanisms. 17 In agreement with Epo-dependent CD71/ TfR up-regulation, overexpression of constitutive active Stat5 in primary erythroblasts, one of the major signaling molecules induced by Epo, led to Epo-independent CD71/TfR upregulation (data not shown).…”

Section: Lnk Inhibits Epo-dependent Erythroblast Differentiationmentioning

confidence: 60%

Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways

Tong

Zhang

Lodish

2005

Blood

190

186

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Section: Lnk Inhibits Epo-dependent Erythroblast Differentiationmentioning

confidence: 60%

Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways

Tong

Zhang

Lodish

2005

Blood

190

186

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“…Among the five remaining CGs with medium expression on ABI plate, three were discarded due to minor reasons: HPRT and PGK (X-chromosomal location) and TFRC (variable expression in hematopoietic cells). 33,34 Among the six additional primer and probe sets, covering four CGs, in-house B2M RQ-PCR set appeared to be suitable since no statistically significant difference between PB and BM was observed. Comparison between normal and leukemic samples was not possible since only four normal samples were tested (see Material and methods).…”

Section: Control Genes For Diagnosis and Mrd Detection By Rq-pcr E Bementioning

confidence: 99%

Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program

et al. 2003

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Real-time quantitative RT-PCR (RQ-PCR) is a sensitive tool to monitor minimal residual disease (MRD) in leukemic patients through the amplification of a fusion gene (FG) transcript. In order to correct variations in RNA quality and quantity and to calculate the sensitivity of each measurement, a control gene (CG) transcript should be amplified in parallel to the FG transcript. To identify suitable CGs, a study group within the Europe Against Cancer (EAC) program initially focused on 14 potential CGs using a standardized RQ-PCR protocol. Based on the absence of pseudogenes and the level and stability of the CG expression, three genes were finally selected: Abelson (ABL), beta-2-microglobulin (B2M), and beta-glucuronidase (GUS). A multicenter prospective study on normal (n ¼ 126) and diagnostic leukemic (n ¼ 184) samples processed the same day has established reference values for the CG expression. A multicenter retrospective study on over 250 acute and chronic leukemia samples obtained at diagnosis and with an identified FG transcript confirmed that the three CGs had a stable expression in the different types of samples. However, only ABL gene transcript expression did not differ significantly between normal and leukemic samples at diagnosis. We therefore propose to use the ABL gene as CG for RQ-PCRbased diagnosis and MRD detection in leukemic patients. Overall, these data are not only eligible for quantification of fusion gene transcripts, but also for the quantification of aberrantly expressed genes.

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“…This regulation explains the increase observed in the expression of TfR1 in erythroid cells in conditions of iron deficiency. 34 However, the respective roles of IRP1 and IRP2 in erythroid cells is not clear since IRP1 knock-out mice have no erythroid phenotype 35 whereas IRP2 knock-out mice develop microcytic hypochromic anemia probably resulting from decreased TfR1 expression in bone marrow cells. 36,37 This standard regulation of iron metabolism seems to have an alternative model during terminal erythroid differentiation.…”

Section: The Iron Sensing Pathwaymentioning

confidence: 99%

Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis

Iolascon¹,

Falco²,

Beaumont³

2009

Haematologica

133

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© F e r r a t a S t o r t i F o u n d a t i o nAIn this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcytosis due to heme synthesis or to iron metabolism defects. Iron and erythropoiesis Iron acquisition pathway in erythroid cellsDeveloping erythroid cells in the bone marrow acquire iron from the plasma iron-transferrin (Tf) complex, through the transferrin receptor (TfR) mediated pathway ( Figure 1). All proliferating cells express transferrin receptors on their cell surface at levels varying from 10 3 to 10 5 molecules per cell. Erythroid precursors, which have an extraordinary requirement for iron to allow for production of hemoglobin, may have over 10 6 transferrin receptors per cell.3 The transferrin-Fe(III) complex in plasma is transported into cells principally through transferrin receptor 1 (TfR1), which is expressed on all dividing cells and is particularly abundant on erythroid precursors. TfR2, encoded by a different gene, is expressed primarily in the liver and binds the transferrin-Fe(III) complex at a much lower affinity than TfR1 and appears to be a signaling molecule rather than an iron transporter. 4 At the pH of the cell surface, TfR1 binds only diferric transferrin. The Tf-Fe(III)/TfR1 complex is internalized into a clathrin-coated pit that, assisted by an adaptor protein complex designated AP-2, 5 rapidly matures to a proton-pumping, pH-lowering endosome. At the lowered pH, iron is released from Tf and subsequently reduced to Fe(II) and transported across the endosomal membrane by Divalent Metal Transporter 1 (DMT1).6 DMT1/Nramp2, a member of the Natural Resistance-Associated-Macrophage Protein (Nramp) family, is a proton-coupled divalent metal transporter found at the plasma membrane and in endosomes of cells of both the duodenum and peripheral tissues. Iron-depleted Tf is then returned to the cell surface where, again encountering a pH of 7.4, the protein is released for another cycle of iron transport. Recently, Steap3 (6-transmembrane epithelial antigen of the prostate 3), an endosomal ferrireductase that facilitates Tf-mediated uptake of iron in erythroid precursors has been identified. 8Steap3 is expressed highly in hematopoietic tissues, colocalizes with the Tf cycle endosome and facilitates Tfbound iron uptake. Erythroid cells from mice deficient in Steap3 (nm1054) are defective in Tf-dependent iron uptake, resulting in a hypochromic, microcytic anemia typical of iron deficiency 9 whereas overexpression of Steap3 stimulates the reduction of iron. Taken together, these findings indicate that Steap3 is an endosomal ferrireductase required for efficient Tf-dependent iron uptake in erythroid cells. However, nml054 and Steap3 −/− erythroid precursors retain some residual ferrireductase as well as iron uptake activity, indicating that there are other ways of reducing iron in the Tf-cycle endosome and/or that there are other endosomal iron transporters that are not res...

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Mechanisms of differential transferrin receptor expression in normal hematopoiesis

Cited by 42 publications

References 65 publications

Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways

Lnk inhibits erythropoiesis and Epo-dependent JAK2 activation and downstream signaling pathways

Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program

Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis

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