Abstract
ABSTRACTObject: To explore the critical role of growth differentiation factor 11 (GDF11) in the pathobiology of aplastic anemia (AA). Methods: We have examined the serum GDF11 levels for 79 AA patients and 30 healthy controls. A total of 79 AA patients, which included 29 new diagnosed (untreated) cases, 14 cases with no response, 21 partial remission (PR) cases and 15 complete remission (CR) cases after immunosuppressive therapy (IST). GDF11 serum levels were assessed by an enzyme-linked immunosorbent assay. GDF11 mRNA expression in peripheral blood mononuclear (PBMNC) was detected through real time polymerase chain reaction. The correlation between GDF11 expression and erythropoietic function was evaluated. Results: The serum GDF11 levels in untreated AA patients were higher than that of the control group. The serum GDF11 levels of PR patients or CR patients after IST was decreased, compared with untreated patients, but did not recover back to the normal levels. GDF11 levels had a negative correlation with hemoglobin (Hb) levels and reticulocyte counts in AA patients. GDF11 levels did not correlate with age, sex and severity of in AA patients. Conclusion: Serum GDF11 levels were increased and negatively correlated with Hb levels and reticulocyte counts in AA patients. This suggests an impaired GDF11 response contributing to anemia in AA patients.
Highlights
Aplastic anemia (AA) is a class of disease characterized by bone marrow failure and pancytopenia
The highest growth differentiation factor 11 (GDF11) levels were observed in 14 AA patients with no response (NR) after immunosuppressive therapy (IST) (131.8 ± 10.80 μg/L)
GDF11 mRNA was overexpressed in peripheral blood mononuclear (PBMNC) of AA patients
Summary
Aplastic anemia (AA) is a class of disease characterized by bone marrow failure and pancytopenia. An immune response dominated by expanded cytotoxic T-cells targets hematopoietic stem (HSC) and progenitor cells (HPC), which induce HSC/HPC apoptosis [2,3]. AA can be successfully treated with either immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) [4]. Cytokines are essential for the viability, proliferation and differentiation of HSC; which include granulocyte colony-stimulating factor (GCSF), granulocyte, macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) [5]. Erythropoiesis is a multistep process by which erythroid precursor cells proliferate and differentiate into mature red blood cells (RBCs). During the early stages of erythropoiesis, erythropoietin (EPO) regulates hematopoietic progenitor cells to differentiate into proerythroblasts [6]
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