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ELife Jun 2023Ribosomal protein (Rp) gene haploinsufficiency can result in Diamond-Blackfan Anemia (DBA), characterized by defective erythropoiesis and skeletal defects. Some mouse Rp...
Ribosomal protein (Rp) gene haploinsufficiency can result in Diamond-Blackfan Anemia (DBA), characterized by defective erythropoiesis and skeletal defects. Some mouse Rp mutations recapitulate DBA phenotypes, although others lack erythropoietic or skeletal defects. We generated a conditional knockout mouse to partially delete 2. Homozygous deletion resulted in embryonic lethality. Mice inheriting the genotype had growth and morphological defects, pancytopenia, and impaired erythropoiesis. A striking reduction in hematopoietic stem cells (HSCs) and progenitors in the bone marrow (BM) was associated with decreased ability to repopulate the blood system after competitive and non-competitive BM transplantation. lost HSC quiescence, experienced ERK and MTOR activation, and increased global translation in HSC and progenitors. Post-natal heterozygous deletion of in hematopoietic cells using Tal1-Cre-ERT also resulted in pancytopenia with decreased HSC numbers. However, post-natal Cre-ERT induction led to reduced translation in HSCs and progenitors, suggesting that this is the most direct consequence of haploinsufficiency in hematopoietic cells. Thus, RpS12 has a strong requirement in HSC function, in addition to erythropoiesis.
Topics: Animals; Mice; Anemia, Diamond-Blackfan; Erythropoiesis; Genes, Essential; Haploinsufficiency; Hematopoietic Stem Cells; Mice, Knockout; Pancytopenia; Ribosomal Proteins
PubMed: 37272618
DOI: 10.7554/eLife.69322 -
JFMS Open Reports 2020A 3-year-old neutered male domestic shorthair cat developed pancytopenia 6 months after starting phenobarbital for treatment of recurrent seizures. The cat was switched...
CASE SUMMARY
A 3-year-old neutered male domestic shorthair cat developed pancytopenia 6 months after starting phenobarbital for treatment of recurrent seizures. The cat was switched from phenobarbital to levetiracetam and complete resolution of the pancytopenia was documented within 10 weeks, consistent with phenobarbital-induced pancytopenia.
RELEVANCE AND NOVEL INFORMATION
While phenobarbital is frequently used as the first-line treatment for seizures in cats, phenobarbital-induced feline pancytopenia has not been documented in the veterinary literature before. Based on this case, regular monitoring of the complete blood count in cats receiving long-term phenobarbital treatment should be considered. In cases of persistent or severe haematological abnormalities, further investigations are required and treatment discontinuation may be needed in the absence of other causes of pancytopenia.
PubMed: 32528719
DOI: 10.1177/2055116920916945 -
Frontiers in Immunology 2023Poor graft function (PGF), manifested by multilineage cytopenias and complete donor chimerism post-allogeneic stem cell transplantation (alloSCT), and acquired aplastic...
Poor graft function (PGF), manifested by multilineage cytopenias and complete donor chimerism post-allogeneic stem cell transplantation (alloSCT), and acquired aplastic anaemia (AA) are immune-mediated acquired bone marrow (BM) failure syndromes with a similar clinical presentation. In this study, we used spatial proteomics to compare the immunobiology of the BM microenvironment and identify common mechanisms of immune dysregulation under these conditions. Archival BM trephines from patients exhibited downregulation of the immunoregulatory protein VISTA and the M2 macrophage marker and suppressor of T-cell activation ARG1 with increased expression of the immune checkpoint B7-H3 compared to normal controls. Increased CD163 and CD14 expression suggested monocyte/macrophage skewing, which, combined with dysregulation of STING and VISTA, is indicative of an environment of reduced immunoregulation resulting in the profound suppression of hematopoiesis in these two conditions. There were no changes in the immune microenvironment between paired diagnostic AA and secondary MDS/AML samples suggesting that leukaemic clones develop in the impaired immune microenvironment of AA without the need for further alterations. Of the eight proteins with dysregulated expression shared by diagnostic AA and PGF, the diagnostic AA samples had a greater fold change in expression than PGF, suggesting that these diseases represent a spectrum of immune dysregulation. Unexpectedly, analysis of samples from patients with good graft function post-alloSCT demonstrated significant changes in the immune microenvironment compared to normal controls, with downregulation of CD44, STING, VISTA, and ARG1, suggesting that recovery of multilineage haematopoiesis post-alloSCT does not reflect recovery of immune function and may prime patients for the development of PGF upon further inflammatory insult. The demonstrable similarities in the immunopathology of AA and PGF will allow the design of clinical interventions that include both patient cohorts to accelerate therapeutic discovery and translation.
Topics: Humans; Proteomics; Bone Marrow; Hematopoietic Stem Cell Transplantation; Bone Marrow Failure Disorders; Anemia, Aplastic; Pancytopenia
PubMed: 37818364
DOI: 10.3389/fimmu.2023.1213560 -
Hematology (Amsterdam, Netherlands) Dec 2022The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no...
OBJECTIVES
The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no assessment of immunological homeostasis. Our study aimed to identify the conditions of establishing a model and assess the AA model in immunology and pathology.
METHODS
We induced an AA mouse model by the combination between sublethal irradiation and spleen-thymus lymphocyte infusion. The success of establishing the AA model was identified by blood routine tests and pathology of bone marrow. The frequency of Th17 and Treg cells was measured by flow cytometry. The frequency of CD34+ and CD41+ cells was detected by immunohistochemical technique.IL-6, IL-8, IL-17, TNF-α and IFN-γ were evaluated by ELISA.
RESULTS
The Cs sublethal irradiation (5 Gy) and spleen-thymus lymphocyte infusion (5 106) induced the AA mouse model successfully. The AA mice had a long lifetime and manifested pancytopenia and bone marrow failure. The percentage of Th17 cells increased and the percentage of Treg cells decreased distinctly in AA mice. The area of hematopoietic tissues and count of CD34+ cells and CD41+ cells were significantly reduced in AA mice.The level of cytokines, IL-6, IL-8, IL-17, TNF-α and IFN-γ, was increased significantly in peripheral blood and bone marrow.
CONCLUSION
Our data suggest that the improved AA mouse model conforms to the diagnosis standard of AA and simulates the immune internal environment of human AA. The AA mouse model has a longer lifetime and unbalances of Th17/Treg cells caused the destruction of CD34+ cells and CD41+ cells, which was immune-mediated pathogenesis to adapt to long-term research.
Topics: Anemia, Aplastic; Animals; Disease Models, Animal; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Mice; Pancytopenia; Spleen; Th17 Cells; Tumor Necrosis Factor-alpha
PubMed: 36004514
DOI: 10.1080/16078454.2022.2113356 -
British Journal of Haematology Dec 2023MECOM-associated syndrome (MECOM-AS) is a rare disease characterized by amegakaryocytic thrombocytopenia, progressive bone marrow failure, pancytopenia and radioulnar...
MECOM-associated syndrome (MECOM-AS) is a rare disease characterized by amegakaryocytic thrombocytopenia, progressive bone marrow failure, pancytopenia and radioulnar synostosis with high penetrance. The clinical phenotype may also include finger malformations, cardiac and renal alterations, hearing loss, B-cell deficiency and predisposition to infections. The syndrome, usually diagnosed in the neonatal period because of severe thrombocytopenia, is caused by mutations in the MECOM gene, encoding for the transcription factor EVI1. The mechanism linking the alteration of EVI1 function and thrombocytopenia is poorly understood. In a paediatric patient affected by severe thrombocytopenia, we identified a novel variant of the MECOM gene (p.P634L), whose effect was tested on pAP-1 enhancer element and promoters of targeted genes showing that the mutation impairs the repressive activity of the transcription factor. Moreover, we demonstrated that EVI1 controls the transcriptional regulation of MPL, a gene whose mutations are responsible for congenital amegakaryocytic thrombocytopenia (CAMT), potentially explaining the partial overlap between MECOM-AS and CAMT.
Topics: Infant, Newborn; Humans; Child; Pancytopenia; Transcription Factors; Thrombocytopenia; Bone Marrow Failure Disorders; Mutation; Receptors, Thrombopoietin; MDS1 and EVI1 Complex Locus Protein
PubMed: 37610030
DOI: 10.1111/bjh.19023 -
Hormones (Athens, Greece) Mar 2021Occurrence of pancytopenia in patients with untreated hyperthyroidism is extremely rare. To the best of our knowledge, only 30 cases have been reported in the English... (Review)
Review
INTRODUCTION
Occurrence of pancytopenia in patients with untreated hyperthyroidism is extremely rare. To the best of our knowledge, only 30 cases have been reported in the English literature. Accurate diagnosis and appropriate tailored therapy are challenging due to the variegated causes of pancytopenia and the potential hematological toxicity of antithyroid drugs (ATDs).
CASE REPORT
We present a 51-year-old Caucasian man with newly diagnosed Graves' disease showing pancytopenia and liver dysfunction. Although in this context the use of ATDs is still under debate, low-dose methimazole therapy was able to induce resolution of both pancytopenia and liver dysfunction, along with euthyroidism restoration.
CONCLUSION
Searching in the English literature for previous studies, we identified only 30 cases worldwide to form our database. A demographic as well as clinical, laboratory, and histopathological analysis was performed. In most cases, the recovery of biochemical euthyroidism through the use of ATDs induced the resolution of pancytopenia (at laboratory and histological levels). Our review provides clinical, laboratory, and histopathological features of Graves's hyperthyroidism-related pancytopenia with a view to improving the knowledge of this rare hematological complication and assisting in the decision-making process regarding therapeutic options.
Topics: Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancytopenia
PubMed: 32638234
DOI: 10.1007/s42000-020-00227-5 -
Cureus Aug 2022Background The etiologies of pancytopenia in the pediatric age group remain exceedingly ubiquitous and warrant extensive hematological and interventional investigations...
Background The etiologies of pancytopenia in the pediatric age group remain exceedingly ubiquitous and warrant extensive hematological and interventional investigations like bone marrow biopsy. It varies widely from benign nutritional disorders to fatal malignancies. The present study aims to delineate the prevalence of various causes of pancytopenia in the pediatric population. Methods The present cross-sectional study included 96 patients between the age of one month till 15 years with pancytopenia. Study participants were evaluated for various parameters including their demographical details, clinical features, immunization history, and nature of the disorder. The prevalence of various etiologies (nutritional, neoplastic, infectious, autoimmune, and others) of pancytopenia was ascertained. Results Of the 96 patients, 42 (43.75%) were males with a mean age of 69.47 ± 7.12 months. Fever was present in 71.87%, arthralgias in 56.25%, weight loss in 35.41%, and failure to thrive in 18.75% of patients. The bone marrow examination revealed aplastic changes in 36 (37.50%), hyperplastic changes in 21 (21.87%), and normal cellularity in 40.62% of patients. Megaloblastic anemia was the most common nutritional cause of pancytopenia present in 21.85% of cases. Acute lymphoblastic leukemia (ALL) was the most prevalent neoplastic etiology present in 19.79% of patients. Aplastic anemia, miliary tuberculosis, parvovirus B19, and hemolytic anemia were other notable etiologies. Conclusion Megaloblastic anemia and infections like tuberculosis were common treatable etiologies of pancytopenia among the pediatric age group. ALL was the most common neoplastic etiology. Bone marrow biopsy remains crucial in elucidating the various neoplastic and nutritional etiologies of pancytopenia in children.
PubMed: 36110464
DOI: 10.7759/cureus.27842 -
Clinical Infectious Diseases : An... Oct 2023
Topics: Humans; Pancytopenia; Transplant Recipients; Cough; Fever; Leishmaniasis, Visceral
PubMed: 37796055
DOI: 10.1093/cid/ciad167 -
Journal of Pediatric Hematology/oncology Mar 2021
Topics: Adolescent; Anemia; Copper; Female; Humans; Lymphopenia; Neutropenia; Pancytopenia; Prognosis
PubMed: 33448718
DOI: 10.1097/MPH.0000000000002047 -
Indian Journal of Gastroenterology :... Apr 2023Pancytopenia in children with celiac disease (CeD) is postulated to be due to nutritional deficiency such as vitamin B, folate and copper or an autoimmune process...
Pancytopenia in children with celiac disease (CeD) is postulated to be due to nutritional deficiency such as vitamin B, folate and copper or an autoimmune process resulting in aplastic anemia with hypoplastic marrow. In the present case series, we report the profile and explore the etiology of pancytopenia among children with CeD. There are only a few case reports of pancytopenia in children with CeD. We enrolled newly diagnosed cases of CeD and pancytopenia presenting in the celiac disease clinic over three years. Detailed evaluation was carried out for the cause of pancytopenia. We followed up on the cases for compliance and response to gluten-free diet at three months, six months and 12 months. Twenty patients were eligible for inclusion. They were divided into two groups: one with aplastic anemia with hypoplastic marrow labeled as Gp CeD-AA and the other with megaloblastic/nutritional anemia labeled as Gp CeD-MA. Patients in Gp CeD-MA presented with classical symptoms of CeD as recurrent diarrhea, abdomen distension, pallor and poor weight gain. They had none or just one transfusion requirement and had an early and complete recovery from pancytopenia. Patients in Gp CeD-AA presented with atypical symptoms such as epistaxis, short stature, fever, pallor and weakness. They had a multiple blood transfusion requirement and had delayed and partial recovery from pancytopenia. Pancytopenia is not a disease in itself but is the presentation of an underlying disease. It can occur due to various coexisting disorders in children with CeD, which can be as simple as nutritional deficiencies to as complex as an autoimmune process or malignancy. CeD should be included in the differential diagnosis of aplastic anemia as CeD and aplastic anemia both have a similar pathological process involving T cell destruction of tissues.
Topics: Humans; Child; Pancytopenia; Anemia, Aplastic; Celiac Disease; Pallor; Anemia, Megaloblastic
PubMed: 37162701
DOI: 10.1007/s12664-022-01327-3