Stage Specific Expression Pattern of Alpha-Hemoglobin-Stabilizing-Protein (AHSP) Portrayed in Erythroblast Chronology

Walczak, Julia; Johnson, Maria D Camargo; Muthumalaiappan, Kuzhali

doi:10.3390/mps3030046

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…AHSP expression gradually increases during erythroid development, peaking at the polychromatic and orthochromatic stages 17 . Walczak et al 20 . recently used imaging flow cytometry to study the development of erythroblasts from healthy donors.…”

Section: Discussionmentioning

confidence: 99%

Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

et al. 2021

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Summary Alpha haemoglobin‐stabilising protein (AHSP) is a key chaperone synthesised in red blood cell (RBC) precursors. Many studies have reported AHSP as a potential biomarker of various diseases. AHSP gene expression has been studied in detail, but little is known about AHSP protein levels in RBCs. We investigated the AHSP concentration of RBC lysates from control subjects (n = 10) and patients with sickle cell anaemia (SCA) with (n = 10) and without (n = 12) hydroxycarbamide (HC) treatment, to evaluate the clinical relevance of AHSP in SCA. We developed a sandwich enzyme‐linked immunosorbent assay method, with which we were able, for the first time, to determine the mean AHSP concentration in control RBC lysates (0·82 µg/ml). The AHSP concentration (2·23 µg/ml) was significantly higher in untreated patients with the SS genotype than in controls. The AHSP concentration decreased significantly on HC treatment (1·50 µg/ml) but remained significantly higher than that in controls. A strong positive correlation was observed between the AHSP concentration and the α‐haemoglobin pool with the three groups of subjects pooled into a single group. Our present findings indicate that AHSP concentration can be considered a candidate biomarker for monitoring HC responses in patients with SCA and suggest a role for AHSP in various RBC diseases.

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Section: Discussionmentioning

confidence: 99%

Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

et al. 2021

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“…AHSP is a cytoplasmic chaperone protein that sequesters free alphahemoglobin and prevents its precipitation during erythropoiesis. 8 Importantly, AHSP expression is seen throughout erythroid development and is absent from non-nucleated red blood cells, 9,10 making it an ideal marker for EBI.…”

Section: Introductionmentioning

confidence: 99%

Digital image analysis of erythroblastic islands in myelodysplastic syndromes

Zhang

Drumheller

Wang

et al. 2023

Int J Lab Hematology

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Introduction Myelodysplastic syndromes (MDS) encompass a diverse group of myeloid neoplasms for which the diagnosis of low‐grade subtypes remains challenging. Erythroblastic islands (EBIs) are highly organized units of erythroid proliferation, differentiation, and enucleation. EBI disruption is frequently observed and is believed to be one of the early changes in MDS. Methods In this study, we digitally analyzed bone marrow biopsies dual stained with alpha‐hemoglobin stabilizing protein (AHSP) and CD163 to quantitatively study features of EBIs in MDS, among MDS subtypes, as well as those in normal marrows and marrows with other causes of anemia. Results EBIs in MDS specimens were smaller in size and higher in density compared to both normal and non‐MDS anemia specimens. Increased CD163 expression within the EBIs is observed in both MDS and other causes of anemia. A combination of increased EBI density and CD163 expression is seen in association with MDS with high‐risk cytogenetics and multiple adverse mutations. Conclusion As a proof‐of‐concept study, we show that EBI features can be relatively easily quantified with AHSP/CD163 dual immunohistochemistry and open‐source imaging analysis software, highlighting those that are unique to MDS, and which may be prognostically relevant. Further studies of the measurable EBI features may provide valuable and novel tools to aid MDS diagnosis and prognostication in the era of digital pathology.

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Transient Improvement in Erythropoiesis Is Achieved Via the Chaperone AHSP With Early Administration of Propranolol in Burn Patients

Walczak

Bunn

Saini

et al. 2020

Journal of Burn Care &Amp; Research

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Burn patients experience erythropoietin resistant anemia in which early commitment and late maturation of erythroblasts are defective. We previously showed that propranolol (Prop) treatment restores erythroid committed progenitors, but terminal maturation remains impaired. Hemoglobinization and maturation occurs during terminal erythropoiesis and these processes are aided by an erythroblast intrinsic functional protein called alpha hemoglobin stabilizing protein (AHSP). We evaluated the role of AHSP in PBMC (peripheral blood mono nuclear cell) derived erythroblasts and the implications of Prop in burn patients. Blood samples were collected at three time points from seventeen patients receiving standard burn care (SBC) or Prop. Five healthy volunteers provided control plasma (CP). PBMCs were placed in biphasic cultures with 5% autologous plasma (BP) or CP. Erythroblasts were harvested during mid and late maturation stages; the percentage of AHSP + erythroblasts, AHSP expression, and relative distribution of reticulocytes and polychromatophilic erythroblasts (PolyE) were determined by cytometry. During the second time point (7-10 days post burn), Prop cohort required 35% less transfusions. At mid maturation, PBMCs from Prop treated patients cultured in BP had 33% more AHSP + erythroblasts and 40% more AHSP expression compared to SBC. Furthermore, at late maturation, Prop had 50% more reticulocytes and 30% less PolyEs in CP versus BP compared to SBC (11% and 6% respectively). AHSP is positively associated with late stage maturation of PBMC derived erythroblasts in the presence of CP. Albeit transiently, this is more pronounced in Prop than SBC. Early administration of propranolol in burn patients supports erythropoiesis via the chaperone AHSP.

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Stage Specific Expression Pattern of Alpha-Hemoglobin-Stabilizing-Protein (AHSP) Portrayed in Erythroblast Chronology

Cited by 3 publications

References 19 publications

Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

Digital image analysis of erythroblastic islands in myelodysplastic syndromes

Transient Improvement in Erythropoiesis Is Achieved Via the Chaperone AHSP With Early Administration of Propranolol in Burn Patients

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