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Best Practice & Research. Clinical... Jun 2021Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune... (Review)
Review
Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune aplastic anemia, the commonest BMF, is a diagnosis of exclusion. In this review, we discuss a general approach to the evaluation of BMF, focusing on clinical presentations particular to immune and various constitutional disorders as well as the interpretation of bone marrow histology, flow cytometry, and karyotyping. Additionally, we examine the role of specialized testing in both immune and inherited BMF, and discuss genetic testing, both its role in patient evaluation and interpretation of results.
Topics: Anemia, Aplastic; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Genetic Testing; Hematology; Humans
PubMed: 34404527
DOI: 10.1016/j.beha.2021.101275 -
The Journal of Veterinary Medical... Jun 2020Non-neoplastic bone marrow disorders such as non-regenerative immune-mediated anemia, pure red cell aplasia, and myelodysplastic syndrome are major causes of...
Non-neoplastic bone marrow disorders such as non-regenerative immune-mediated anemia, pure red cell aplasia, and myelodysplastic syndrome are major causes of non-regenerative anemia in dogs. However, there has been no study on the clinical and clinicopathological features of canine non-neoplastic bone marrow disorders in Japan. Hence, we first investigated the breed disposition of non-neoplastic bone marrow disorders that induce anemia as a retrospective study and found that Miniature Dachshund (MD) was a predisposed breed. Based on this finding, we investigated the clinical and clinicopathological features of non-neoplastic bone marrow disorders in MDs as a preliminary retrospective study, and we compared them between immunosuppressive treatment-responsive and -resistant MDs. We found that treatment-resistant MDs showed thrombocytosis and increased frequencies of dysplastic features in the peripheral blood. These results indicate that bone marrow disorders in treatment-resistant MDs might manifest distinct features compared with those in treatment-sensitive MDs, and sensitivity to immunosuppressive treatments could be predicted based on thrombocytosis and dysplastic features in the peripheral blood. Further studies that examine aberrations in the genome are needed to elucidate the pathophysiology of bone marrow disorders in MDs.
Topics: Anemia, Hemolytic; Animals; Bone Marrow Diseases; Dog Diseases; Dogs; Female; Genetic Predisposition to Disease; Glucocorticoids; Immunosuppressive Agents; Japan; Male; Prednisolone; Retrospective Studies; Species Specificity; Treatment Outcome
PubMed: 32307340
DOI: 10.1292/jvms.19-0439 -
Journal of Bone and Mineral Research :... Apr 2017Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with... (Meta-Analysis)
Meta-Analysis Review
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis. The effect of the disease state on bone density was significant and negative for beta-thalassemia (r = -2.00; 95% confidence interval [CI] -3.41, -0.58; p < 0.005), sickle cell anemia (-0.91; -1.36, -0.47; p < 0.00005), chronic myelogenous leukemia (-0.55; -0.88, -0.22; p < 0005), mastocytosis (-0.99; -1.16, -0.82; p < 0.00001), lymphoblastic leukemia (-0.69; -0.98, -0.40; p < 0.00001), multiple myeloma (-0.67; -0.99, -0.35; p < 0.00005), and hemochromatosis (-1.15; -1.64, -0.66; p < 0.00001). The changes were negative but not significant for polycythemia vera (-0.16; -0.38, 0.05; p = 0.069) and essential thrombocythemia (-0.33; -0.92, 0.26; p = 0.14). In myelofibrosis, disease state was associated with increased bone density (0.74; 0.12, 1.36; p < 0.05). Bone density change significantly and negatively correlated with the level of ferritin and bone marrow cellularity but not with hemoglobin or erythropoietin. Thus, independent of hematopoietic lineage, abnormal proliferation of bone marrow cells appears to be associated with bone loss. Iron metabolism may independently contribute to bone homeostasis. © 2016 American Society for Bone and Mineral Research.
Topics: Bone Density; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; Cell Proliferation; Female; Ferritins; Homeostasis; Humans; Male
PubMed: 27787922
DOI: 10.1002/jbmr.3026 -
Seminars in Hematology Jan 2022Fanconi anemia, telomeropathies and ribosomopathies are members of the inherited bone marrow failure syndromes, rare genetic disorders that lead to failure of... (Review)
Review
Fanconi anemia, telomeropathies and ribosomopathies are members of the inherited bone marrow failure syndromes, rare genetic disorders that lead to failure of hematopoiesis, developmental abnormalities, and cancer predisposition. While each disorder is caused by different genetic defects in seemingly disparate processes of DNA repair, telomere maintenance, or ribosome biogenesis, they appear to lead to a common pathway characterized by premature senescence of hematopoietic stem cells. Here we review the experimental data on senescence and inflammation underlying marrow failure and malignant transformation. We conclude with a critical assessment of current and future therapies targeting these pathways in inherited bone marrow failure syndromes patients.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Cellular Senescence; Congenital Bone Marrow Failure Syndromes; Fanconi Anemia; Humans
PubMed: 35491056
DOI: 10.1053/j.seminhematol.2022.01.003 -
Current Opinion in Pediatrics Feb 2023Recent advances in diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have significantly improved disease understanding and patient outcomes.... (Review)
Review
PURPOSE OF REVIEW
Recent advances in diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have significantly improved disease understanding and patient outcomes. Still, IBMFS present clinical challenges that require further progress. This review aims to provide an overview of the current state of diagnosis and treatment modalities of the major IBMFS seen in paediatrics and present areas of prioritization for future research.
RECENT FINDINGS
Haematopoietic cell transplantation (HCT) for IBMFS has greatly improved in recent years, shifting the research and clinical focus towards cancer predispositions and adverse effects of treatment. Each year, additional novel genes and pathogenic variants are described, and genotype-phenotype mapping becomes more sophisticated. Moreover, novel therapeutics exploring disease-specific mechanisms show promise to complement HCT and treat patients who cannot undergo current treatment options.
SUMMARY
Research on IBMFS should have short-term and long-term goals. Immediate challenges include solidifying diagnostic and treatment guidelines, cancer detection and treatment, and continued optimization of HCT. Long-term goals should emphasize genotype-phenotype mapping, genetic screening tools and gene-targeted therapy.
Topics: Child; Humans; Anemia, Aplastic; Bone Marrow Diseases; Congenital Bone Marrow Failure Syndromes; Fanconi Anemia; Bone Marrow Failure Disorders; Hemoglobinuria, Paroxysmal
PubMed: 36354296
DOI: 10.1097/MOP.0000000000001196 -
Archives of Pathology & Laboratory... Apr 2008Examination of the bone marrow poses several unique challenges to the pathologist: it is a semisolid organ without helpful gross correlation, it exists in a dynamic... (Review)
Review
Examination of the bone marrow poses several unique challenges to the pathologist: it is a semisolid organ without helpful gross correlation, it exists in a dynamic state with the peripheral blood and other organs of the lymphohemopoietic system, and the diagnosis of diseases affecting bone marrow often depends heavily on ancillary special studies. The bone marrow examination ideally encompasses review of the bone marrow biopsy histology (with or without additional nondecalcified clot preparation material), bone marrow aspirate smear cytology, and the peripheral blood smear; optimal procurement and processing of these samples is critical in ensuring that a maximal level of diagnostic information can be extracted. The pathologist must be aware of the clinical context of the bone marrow and the results of ancillary tests, whether these are ordered by the pathologist or the clinician. A combination of excellent diagnostic samples, appropriate ancillary tests, and knowledge of the clinical context provides the best background to distinguish between the common reactive and neoplastic processes that involve the bone marrow and to avoid diagnostic pitfalls in making these distinctions.
Topics: Biopsy; Bone Marrow; Bone Marrow Diseases; Bone Marrow Examination; Bone Marrow Neoplasms; Diagnosis, Differential; Humans; Pathology
PubMed: 18384210
DOI: 10.5858/2008-132-587-RVNBMP -
Annals of Medicine Sep 2014The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples... (Review)
Review
The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed.
Topics: Adolescent; Adult; Anemia, Aplastic; Anemia, Diamond-Blackfan; Bone Marrow Diseases; Bone Marrow Failure Disorders; Congenital Bone Marrow Failure Syndromes; Dyskeratosis Congenita; Exocrine Pancreatic Insufficiency; Fanconi Anemia; Hemoglobinuria, Paroxysmal; Humans; Lipomatosis; Neutropenia; Radius; Shwachman-Diamond Syndrome; Thrombocytopenia; Upper Extremity Deformities, Congenital; Young Adult
PubMed: 24888387
DOI: 10.3109/07853890.2014.915579 -
Mutation Research Feb 2012Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of telomere-mediated disorders. Germline mutations in the essential telomerase genes, hTERT and hTR,... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of telomere-mediated disorders. Germline mutations in the essential telomerase genes, hTERT and hTR, are the causal genetic defect in up to one-sixth of pulmonary fibrosis families. The presence of telomerase mutations in this subset is significant for clinical decisions as affected individuals can develop extra-pulmonary complications related to telomere shortening such as bone marrow failure and cryptogenic liver cirrhosis. There is also evidence that IPF is an ancestral manifestation of autosomal dominant telomere syndromes where, with successive generations, the disease evolves from pulmonary fibrosis into a bone marrow failure-predominant disorder, defining a unique form of genetic anticipation. Here I review the significance of telomere defects for understanding the genetics, disease patterns and pathophysiology of IPF. The importance of this diagnosis for patient care decisions will also be discussed.
Topics: Age Factors; Bone Marrow Diseases; Dyskeratosis Congenita; Emphysema; Genes, Dominant; Genetic Predisposition to Disease; Humans; Pulmonary Fibrosis; Telomerase; Telomere Shortening
PubMed: 22079513
DOI: 10.1016/j.mrfmmm.2011.10.013 -
Journal of Clinical and Experimental... 2018Bone marrow failure (BMF) is a rare but life-threatening disorder that usually manifests as (pan)cytopenia. BMF can be caused by a variety of diseases, but inherited BMF... (Review)
Review
Bone marrow failure (BMF) is a rare but life-threatening disorder that usually manifests as (pan)cytopenia. BMF can be caused by a variety of diseases, but inherited BMF (IBMF) syndromes are a clinically important cause, especially in children. IBMF syndromes are a heterogeneous group of genetic disorders characterized by BMF, physical abnormalities, and predisposition to malignancy. An accurate diagnosis is critical, as disease-specific management, surveillance, and genetic counselling are required for each patient. The major differential diagnoses of IBMF syndromes are acquired aplastic anemia (AA) and refractory cytopenia of childhood (RCC). These diseases have overlapping features, such as BM hypocellularity and/or dysplastic changes, which make the differential diagnosis challenging. RCC has been defined as a histomorphologically distinct entity. Therefore, understanding the BM histopathology of these diseases is essential for the differential diagnosis. However, the BM histopathological features have not been characterized in detail, as descriptions of BM histopathology are very limited due to the rarity of the diseases. This review provides a detailed description of the BM histopathology in cases of RCC, AA, and the four most common IBMF syndromes: Fanconi anemia (FA), dysketatosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS). An overview, including the clinical features and diagnosis, is also provided.
Topics: Adolescent; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Child, Preschool; Diagnosis, Differential; Female; Hemoglobinuria, Paroxysmal; Histological Techniques; Humans; Infant; Male
PubMed: 29998978
DOI: 10.3960/jslrt.18018 -
Hematology/oncology Clinics of North... Aug 2018Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to... (Review)
Review
Dyskeratosis congenita (DC) is a rare, inherited bone marrow failure (BMF) syndrome characterized by variable manifestations and ages of onset, and predisposition to cancer. DC is one of a spectrum of diseases caused by mutations in genes regulating telomere maintenance, collectively referred to as telomere biology disorders (TBDs). Hematologic disease is common in children with DC/TBD. Timely diagnosis of underlying TBD in patients with BMF affects treatment and has been facilitated by increased awareness and availability of diagnostic tests in recent years. This article summarizes the pathophysiology, evaluation, and management of hematopoietic failure in patients with DC and other TBDs.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Child, Preschool; Dyskeratosis Congenita; Genetic Predisposition to Disease; Hemoglobinuria, Paroxysmal; Humans; Mutation; Neoplasms; Telomere; Telomere Homeostasis
PubMed: 30047419
DOI: 10.1016/j.hoc.2018.04.003