Serum Hepcidin Level in Patients with Acute Lymphoblastic Leukemia (ALL) during The Treatment Phase: Their Effects on Erythropoisis Activity and Iron Reserves (original) (raw)
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Advances in Hematology, 2011
Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre-and post-HCT was present in all patients. Median hepcidin pre-and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ng/mL) (P < .0001). Liver and renal function, prior chemotherapies, and conditioning had no impact on hepcidin. Despite higher total BU after HCT compared to pretransplantation (P < .0005), pre-and posttransplant ferritin and hepcidin were similar. BU influenced ferritin (P = .001) and hepcidin (P = .001). No correlation of pre-or posttransplant hepcidin with pretransplant ferritin was found. HFE genotype did not influence hepcidin. Conclusions. Hepcidin is elevated in AML patients pre-and post-HCT due to transfusional iron-loading suggesting that hepcidin synthesis remains intact despite chemotherapy and HCT.
Serum Hepcidin Level and Disease Course of Acute Leukemia in Children
The Egyptian Journal of Biochemistry and Molecular Biology
Acute leukemia (AL) is a heterogeneous group of hematopoietic neoplasms and it is the most common childhood malignancy. Many patients with AL develop severe anemia that requires multiple blood transfusions. Hepcidin expression may play a role in anemia which is often seen in these patients. The aim of this study is to evaluate the role of hepcidin in acute lymphoblastic leukemia in children in Egypt. 60 patients with acute lymphoblastic leukemia (ALL) and 20 age and gender matched healthy children, taken as control group, were included in the study. Complete blood count (CBC), Serum ALT and serum AST were measured by colorimetric methods. Serum hepcidin and ferritin were measured by ELISA. The study showed a significant difference between newly diagnosed ALL cases and other groups regarding all CBC parameters. There was a significant difference in serum levels of hepcidin and ferritin between studied groups. A significant negative correlation was found between serum level of hepcidin and ferritin and each of hemoglobin level and reticulocytic count %, while significant positive correlation was found between hepcidin and ferritin serum levels. From this study, it could be concluded that serum hepcidin level is elevated in ALL children patients at time of diagnosis and correlates with the disease extent. Hepcidin may be one of the serum markers that accounting for anemia associated with ALL in children.
Hepcidin levels and their determinants in different types of myelodysplastic syndromes
PloS one, 2011
Iron overload may represent an additional clinical problem in patients with Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone, may play a role, but studies until now have been hampered by technical problems. Using a recently validated assay, we measured serum hepcidin in 113 patients with different MDS subtypes. Mean hepcidin levels were consistently heterogeneous across different MDS subtypes, with the lowest levels in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant predictors of hepcidin in multivariate analyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patients had the highest levels of toxic no...
European Journal of Haematology, 2013
Inhibition of hepcidin expression by erythropoietic signals is of great physiological importance; however, the inhibitory pathways remain poorly understood. To investigate (i) the direct effect of erythropoietin (Epo) and (ii) the contribution of putative mediators on hepcidin repression, healthy volunteers were injected with a single dose of Epo, either low (63 IU/kg, n = 8) or high (400 IU/kg, n = 6). Low-dose Epo provoked hepcidin down-modulation within 24 h; the effect was not immediate as hepcidin circadian variations were still present following injection. High-dose Epo induced no additional effect on the hepcidin response, that is hepcidin diurnal fluctuations were not abolished in spite of extremely high Epo levels. We did not find significant changes in putative mediators of hepcidin repression, such as transferrin saturation, soluble transferrin receptor, or growth differentiation factor 15. Furthermore, the potential hepcidin inhibitor, soluble hemojuvelin, was found unaltered by Epo stimulation. This finding was consistent with the absence of signs of iron deficiency observed at the level of skeletal muscle tissue. Our data suggest that hepcidin repression by erythropoietic signals in humans may not be controlled directly by Epo, but mediated by a still undefined factor.
IJSRP
Iron deficiency is mostly affecting nutritional deficiency in low and middle-income countries. Infants, young children, adolescent females, young females with heavy bleeding during menstrual periods, women of childbearing age, and old people are at a significant risk of iron deficiency. Doctors usually prescribe iron therapy in treating iron deficiency. Along with iron deficiency, iron overload is a serious complication when there is an excess of iron storage in the human body. Hemochromatosis, a hereditary genetic defect where an excess of iron absorption happens, caused primary iron overload. Iron overload also develops secondary to multiple transfusions in transfusion-dependent anemic patients (thalassemia, Myelodysplastic syndromes, etc.). Iron overload can damage organs, including the heart and liver, leading to serious complications if it is inadequate or lacks iron chelation therapy. Cytokines and acute phase proteins play a significant role in the etiology of anemia of chronic disease, which is also known as anaemia of inflammation. Hepcidin a peptide hormone regulates iron efflux from plasma-absorbing enterocytes, iron-recycling macrophages, and iron-storing hepatocytes. Hepcidin binds to its receptor ferroportin, a cellular iron exporter, and regulates the membrane content of ferroportin and ferroportin-mediated iron transfer to blood plasma. In iron deficiency, hepcidin reduces iron efflux into the plasma and promotes iron-dependent erythropoiesis. Inflammatory stimuli promote the production of hepcidin, which reduces iron intake in inflammatory anaemia. Hepcidin deficiency results in iron overload in hereditary hemochromatosis, whereas excess hepcidin is associated with inflammatory anaemia, chronic renal disease and iron-refractory anaemia, leading to iron deficiency anemia. The mechanism of hemochromatosis is because of impaired synthesis of hepcidin or impaired hepcidin binding to ferroportin. Hematology parameters and iron studies have limits in diagnosing iron deficiency anaemia , anaemia caused by chronic disorders, according to several studies, as both conditions can produce similar laboratory results. This paper reviews the importance of hepcidin in making a thorough diagnosis of anemia, before starting the treatment, along with serum hepcidin as a prognostic tool for the early detection of early response to oral iron therapy and iron overload (hemochromatosis). Current therapeutic options are limited to control iron levels by regulating the hepcidin/ferroportin axis. This literature review includes reviewing a summary of some of the research in advanced clinical studies on various aspects of hepcidin tuning, understanding the mechanism of hepcidin and its pathological components which may lead to advanced therapies, and alternative therapies, along with the importance of new treatment options, including modulation and inhibition of hepcidin activity and its future use in clinical trials and implementing the latest treatment options. Methodology: The information was collected from secondary sources published in various scholarly journals selected from google scholar. The research articles systematically reviewed and identified hepcidin's role in iron homeostasis, therapeutic and diagnostic advances, and research gaps in the research field. Results/Findings: Based on a systematic review, the current status of the management of iron homeostasis and its limitations are identified. Hepcidin's role in the diagnostic and therapeutic field is explained. Future advances and research gaps in the management of iron homeostasis are explained in the literature review.
2010
Background. It has been suggested that hepcidin may be useful as a tool for managing iron therapy in haemodialysis (HD) patients on erythropoiesis-stimulating agents (ESA). Methods. We used SELDI-TOF mass spectrometry assay to measure serum hepcidin-25 (Hep-25) and hepcidin-20 (Hep-20) in 56 adult HD patients on maintenance ESA to assess their ability to predict haemoglobin (Hb) response after 1 g intravenous iron (62.5 mg ferric gluconate at 16 consecutive dialysis sessions) and their relationship with markers of iron status, inflammation and erythropoietic activity. Results. At multivariate analysis (in a model that also included Hb, reticulocyte, ESA dose, HFE genotype, soluble transferrin receptor [sTfR] and C-reactive protein), Hep-25 independently correlated with ferritin (β = 0.03, P = 0.01) and the percentage of hypochromic red blood cells [%Hypo] (β = 1.84, P = 0.01), suggesting that Hep-25 may be a useful biomarker for iron stores and bone marrow iron availability. Hep-20 correlated independently with Hep-25 (β = 0.159, P <0.001) and ferritin (β = 0.006, P = 0.05), suggesting that it may be a useful additional biomarker for iron stores. On receiver operating characteristics curve analysis, neither Hep-25 nor Hep-20 significantly predicted who will increase their Hb after iron loading (AUC = 0.52 ± 0.09 and 0.54 ± 0.08, P = 0.612), and the same applied to ferritin and transferrin saturation (AUC = 0.55 ± 0.08 and 0.59 ± 0.08, P = 0.250), whereas %Hypo and reticulocyte Hb content were significant predictors (AUC = 0.84 ± 0.05 and 0.70 ± 0.08, P <0.01). At multivariate logistic regression analysis, %Hypo was the only biomarker independently associated with iron responsiveness. Conclusions. Although our study suggests an important role for hepcidin in regulating iron homeostasis in HD patients on ESA, our findings do not support its utility as a predictor of iron needs, offering no advantage over established markers of iron status.
Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children
Blood, 2012
anemic African children Hepcidin is the major predictor of erythrocyte iron incorporation in http://bloodjournal.hematologylibrary.org/content/119/8/1922.full.html Updated information and services can be found at: (485 articles) Red Cells, Iron, and Erythropoiesis (277 articles) Pediatric Hematology (149 articles) Editorials Articles on similar topics can be found in the following Blood collections http://bloodjournal.
Correlation of Hepcidin to Other Markers of Iron Overload in Egyptian Thalassemia Patients
The Egyptian Journal of Hospital Medicine
Background: Beta thalassemia is a disorder of hemoglobin leading to hemolytic anemia, ineffective erythropoiesis and iron overload that mediates much of the morbidity and mortality of the disease. Hepcidin is a peptide hormone that plays a crucial role in iron homeostasis. Objectives: Here we assessed the value of serum hepcidin level as a marker of iron overload in thalassemia patients. Patients and Methods: This case control study involved 30 thalassemia patients and 10 controls. The patients were selected from the Hematology Department of Ain Shams University Hospitals. We assessed the value of serum hepcidin level and see how it is correlated to values of serum ferritin along with MRI T2*on the liver and the heart in the same patients. Results: The median hepcidin level for cases was significantly lower than that for controls with P value (0.004), but serum hepcidin was not a statistically significant marker of iron overload when correlated with either serum ferritin or hepatic and/or cardiac MRI T2* findings of the patients. However, we found a significant correlation between hepcidin and gender, blood transfusion frequency and hepatitis C infection. Conclusion: hepcidin is not directly correlated to markers of iron overload in thalassemia patients. In these patients with anemia and iron overload, the erythropoietic drive is the dominant factor influencing hepcidin levels. Therefore, hepcidin is not a good marker of iron overload, but rather a good marker of erythropoietic drive.
A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis
2011
Background Inadequate hepcidin production leads to iron overload in nearly all types of hemochromatosis. We explored the acute response of hepcidin to iron challenge in 25 patients with HFEhemochromatosis, in two with TFR2-hemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y homozygotes, 6 C282Y/H63D compound heterozygotes) had increased iron stores, while nine (6 C282Y/C282Y homozygotes, 3 C282Y/H63D compound heterozygotes) were studied after phlebotomy-induced normalization of iron stores. Design and Methods We analyzed serum iron, transferrin saturation, and serum hepcidin by both enzyme-linked immunosorbent assay and mass-spectrometry at baseline, and 4, 8, 12 and 24 hours after a single 65-mg dose of oral iron. Results Serum iron and transferrin saturation significantly increased at 4 hours and returned to baseline values at 8-12 hours in all groups, except in the iron-normalized patients who showed the highest and longest increase of both parameters. The level of hepcidin increased significantly at 4 hours and returned to baseline at 24 hours in controls and in the C282Y/H63D compound heterozygotes at diagnosis. The hepcidin response was smaller in C282Y-homozygotes than in controls, barely detectable in the patients with iron-depleted HFE-hemochromatosis and absent in those with TFR2-hemochromatosis. Conclusions Our results are consistent with a scenario in which TFR2 plays a prominent and HFE a contributory role in the hepcidin response to a dose of oral iron. In iron-normalized patients with HFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.
The Role of Erythropoiesis on Hepcidin Level in Polytransfused b-Thalassemia Major Patients
The Medical Journal of Cairo University, 2018
Background: Hepcidin peptide hormone is a main controller of iron homeostasis, itbecomes elevated in case of iron overload, however despite iron overload in β-Thalassemia major (β-TM) patients a contradictory decrease in Hepcidin occurs. The incompatible Hepcidin level is the main responsible factor causing the iron overload status in iron-loading anemias such as (β-TM) which contributes to organ dysfunctionand to iron toxicity. Aim of Study: To evaluate the conflicting effect of increased erythropoiesis in contrast to the effect of iron overloading on Hepcidin serum level and its correlation with iron status in (β-TM) patients. Subjects and Methods: For all patients and controls Complete Blood Count (CBC), serum assaysof Hepcidin, iron, ferritin, transferrin, HCVAbs, HBs Ag, CRP and serum level were performed. Results: Hepcidin level was significantly lowered in (β-TM) patients compared to controls with high significant difference (p=0.00). There was no correlation between serum Hepcidin and ferritin level, neither was between Hepcidin and serum iron, transferrin, Hb level and reticulocyte count in the study group. Hepcidin/Ferritin ratio showed high significance difference (p<0.000) with mean value in the study group 0.056 vs. 4.75 in controls pointing to an incompatible levels of Hepcidin to iron overload status. Hepcidin level wasnegative correlatedwith age (p<0.05). Conclusion: Hepcidin was markedly decreased in the study group with no significant correlation between serum Hepcidin and ferritin level as a marker of iron overload in thalassemia major. Hepcidin deficiency is the main contributing factor of iron overload in β thalassemia which results from a strong suppressive effect of the high erythropoietic activity on Hepcidin expression. Hepcidin-ferritin ratio was markedly depressed <1 in all β thalassemia major patients which indi