Circulating Erythropoietin in Patients with Acquired Aplastic Anaemia

Kojima, Seiji; Matsuyama, Takaharu; Kodera, Yoshihisa

doi:10.1159/000203992

Cited by 4 publications

(2 citation statements)

References 9 publications

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“…9a ). The Epo-concentration range affecting cell size, from 0.01 to 10 Units/ml, corresponds to the entirety of the physiological and stress range in vivo 57 , 58 . Higher Epo also increased reticulocyte size heterogeneity (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis

et al. 2021

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The erythroid terminal differentiation program couples sequential cell divisions with progressive reductions in cell size. The erythropoietin receptor (EpoR) is essential for erythroblast survival, but its other functions are not well characterized. Here we use Epor−/− mouse erythroblasts endowed with survival signaling to identify novel non-redundant EpoR functions. We find that, paradoxically, EpoR signaling increases red cell size while also increasing the number and speed of erythroblast cell cycles. EpoR-regulation of cell size is independent of established red cell size regulation by iron. High erythropoietin (Epo) increases red cell size in wild-type mice and in human volunteers. The increase in mean corpuscular volume (MCV) outlasts the duration of Epo treatment and is not the result of increased reticulocyte number. Our work shows that EpoR signaling alters the relationship between cycling and cell size. Further, diagnostic interpretations of increased MCV should now include high Epo levels and hypoxic stress.

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Section: Resultsmentioning

confidence: 99%

EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis

et al. 2021

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“…We found that cell size was increased in an Epo-concentrationdependent manner, with larger cells at every stage of differentiation, including reticulocytes (Fig 6b, Extended Data Fig 8a). The Epo concentration range affecting cell size, from 0.01 to 10 Units/ml, covers the entirety of the physiological and stress range that is found for Epo in vivo 66,67 . In addition to increasing reticulocyte diameter, higher Epo concentration also increased reticulocyte size distribution, as shown by respective coefficients of variation of the diameters, making them more heterogeneous (Extended Data Fig 8b).…”

Section: Epo Increases Cell Size and Prolongs Erythroid Maturation Ovmentioning

confidence: 96%

The Erythropoietin Receptor Stimulates Rapid Cycling and Formation of Larger Red Cells During Mouse and Human Erythropoiesis

Hidalgo

Bejder

Pop

et al. 2020

Preprint

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Erythroid terminal differentiation entails cell divisions that are coupled to progressive decreases in cell size. EpoR signaling is essential for the survival of erythroid precursors, but it is unclear whether it has other functions in these cells. Here we endowed mouse precursors that lack the EpoR with survival signaling, finding that this was sufficient to support their differentiation into enucleated red cells, but that the process was abnormal. Precursors underwent fewer and slower cell cycles and yet differentiated into smaller red cells. Surprisingly, EpoR further accelerated cycling of early erythroblasts, the fastest cycling cells in the bone marrow, while simultaneously increasing their cell size. EpoR-mediated formation of larger red cells was independent of the established pathway regulating red cell size by iron through Heme-regulated eIF2α kinase (HRI). We confirmed the effect of Epo on red cell size in human volunteers, whose mean corpuscular volume (MCV) increased following Epo administration. This increase persisted after Epo declined and was not the result of increased reticulocytes. Our work reveals a unique effect of EpoR signaling on the interaction between the cell cycle and cell growth. Further, it suggests new diagnostic interpretations for increased red cell volume, as reflecting high Epo and erythropoietic stress.

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Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme‐linked immunosorbent assay

Kojima

Matsuyama

Kodera³

et al. 1997

Br J Haematol

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Summary.We measured the endogenous plasma concentration of thrombopoietin (TPO) in 76 patients with acquired aplastic anaemia (AA) by a sensitive sandwich enzymelinked immunosorbent assay (ELISA). The plasma TPO concentrations were significantly higher in AA patients when compared to healthy control subjects (P < 0 . 0001) and there was a significant negative correlation between plasma TPO concentrations and platelet counts in 54 AA patients who had not received any platelet transfusions prior to sampling. On the other hand, there was no statistically significant correlation between the TPO concentrations and platelet counts in 22 AA patients who had previously received platelet transfusions.We studied serial changes of plasma TPO concentration in 24 patients who showed an increase in their platelet counts following bone marrow transplantation or immunosuppressive (IS) therapy. Although a decrease in plasma TPO concentration was observed, levels remained above the range of normal healthy controls even in the patients who attained normal platelet counts following therapy. A decrease in TPO concentrations was observed in only half of the responders to IS therapy. Whether exogenous TPO will result in increased platelet counts in AA patients with high TPO levels remains to be determined.

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Circulating Erythropoietin in Patients with Acquired Aplastic Anaemia

Cited by 4 publications

References 9 publications

EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis

EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis

The Erythropoietin Receptor Stimulates Rapid Cycling and Formation of Larger Red Cells During Mouse and Human Erythropoiesis

Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme‐linked immunosorbent assay

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