Tanno T.,Molecular Medicine Branch |
Noel P.,U.S. National Institutes of Health |
Miller J.L.,Molecular Medicine Branch
Current Opinion in Hematology | Year: 2010
PURPOSE OF REVIEW: Growth differentiation factor 15 (GDF15) was identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. This review addresses the regulation, expression and potential functions of GDF15 in the context of erythroid biology. RECENT FINDINGS: GDF15 expression during late erythroid differentiation was discovered as part of an erythroblast transcriptome project. As GDF15 expression is associated with cellular stress or apoptosis, further investigation of the cytokine was focused upon its involvement in ineffective erythropoiesis. Remarkably high serum levels were detected in patients with thalassemia syndromes, congenital dyserythropoiesis and some acquired sideroblastic anemias. High-level GDF15 expression is not a feature of normal erythropoiesis, or erythroid recovery after bone-marrow transplantation. As GDF15 is a transforming growth factor-β superfamily member, it was investigated as an effector of ineffective erythropoiesis that suppresses hepcidin expression despite iron overloading. SUMMARY: In contrast to the low levels of GDF15 expressed during normal erythropoiesis, ineffective erythropoiesis causes high-level expression of GDF15. In patients with thalassemia and related anemias, GDF15 expression may contribute to iron overloading or other features of the disease phenotype. © 2010 Lippincott Williams & Wilkins, Inc.
Rogers H.,Molecular Medicine Branch |
Wang L.,Molecular Medicine Branch |
Yu X.,Molecular Medicine Branch |
Yu X.,University of California at San Francisco |
And 8 more authors.
Journal of Biological Chemistry | Year: 2012
Background: Erythropoietin is required for erythrocyte production and stimulates erythroid gene expression including EPO-R. Results: TAL1 induction promotes accessibility of EPO-R promoter to the GATA-1-TAL1-LMO2-LDB1 transcription activation complex to increase EPO-R expression. Conclusion: Forced TAL1 expression increases EPO-R and erythropoietin hypersensitivity in erythroid progenitors. Significance: Providing insight into the molecular link between TAL1 and erythropoietin activity.
Tanno T.,Molecular Medicine Branch |
Rabel A.,Molecular Medicine Branch |
Lee Y.T.,Molecular Medicine Branch |
Yau Y.Y.,Molecular Medicine Branch |
And 2 more authors.
Transfusion | Year: 2010
Background: Low serum hepcidin levels provide a physiologic response to iron demand in patients with iron deficiency (ID). Based on a discovery of suppressed hepcidin expression by a cytokine named growth differentiation factor 15 (GDF15), it was hypothesized that GDF15 may suppress hepcidin expression in humans with ID due to blood loss. Study Design and Methods: To test this hypothesis, GDF15 and hepcidin levels were measured in peripheral blood from subjects with iron-deficient erythropoiesis before and after iron supplementation. Results: Iron variables and hepcidin levels were significantly suppressed in iron-deficient blood donors compared to healthy volunteers. However, ID was not associated with elevated serum levels of GDF15. Instead, iron-deficient subjects' GDF15 levels were slightly lower than those measured in the control group of subjects (307 ± 90 and 386 ± 104 pg/mL, respectively). Additionally, GDF15 levels were not significantly altered by iron repletion. Conclusions: ID due to blood loss is not associated with a significant change in serum levels of GDF15. © 2010 American Association of Blood Banks.