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Hematology. American Society of... Dec 2017Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure... (Review)
Review
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events. Diamond-Blackfan anemia is commonly treated with corticosteroids, but most patients eventually become refractory to this treatment and toxicity is limiting. Growth factors still have a role in inherited cases, especially granulocyte colony-stimulating factor in congenital neutropenias. Novel therapies are warranted and thrombopoietin receptor agonists, leucine, quercetin, and novel gene therapy approaches may benefit inherited cases in the future.
Topics: Androgens; Bone Marrow Diseases; Chemical and Drug Induced Liver Injury; Danazol; Female; Genetic Diseases, Inborn; Genetic Therapy; Humans; Leucine; Oxymetholone; Quercetin; Stem Cell Transplantation; Syndrome; Virilism
PubMed: 29222242
DOI: 10.1182/asheducation-2017.1.96 -
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 -
Seminars in Fetal & Neonatal Medicine Feb 2016The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of... (Review)
Review
The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond-Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations.
Topics: 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; Infant, Newborn; Lipomatosis; Neutropenia; Radius; Shwachman-Diamond Syndrome; Thrombocytopenia; Upper Extremity Deformities, Congenital
PubMed: 26724991
DOI: 10.1016/j.siny.2015.12.003 -
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 -
Blood Jan 2014The inherited bone marrow failure (BMF) syndromes are a rare and diverse group of genetic disorders that ultimately result in the loss of blood production. The molecular... (Review)
Review
The inherited bone marrow failure (BMF) syndromes are a rare and diverse group of genetic disorders that ultimately result in the loss of blood production. The molecular defects underlying many of these conditions have been elucidated, and great progress has been made toward understanding the normal function of these gene products. This review will focus on perhaps the most well-known and genetically heterogeneous BMF syndrome: Fanconi anemia. More specifically, this account will review the current state of our knowledge on why the bone marrow fails in this illness and what this might tell us about the maintenance of bone marrow function and hematopoiesis.
Topics: Animals; Bone Marrow; Bone Marrow Diseases; Bone Marrow Transplantation; Cross-Linking Reagents; DNA Damage; DNA Repair; Fanconi Anemia; Fanconi Anemia Complementation Group Proteins; Humans; Mice; Stem Cells
PubMed: 24200684
DOI: 10.1182/blood-2013-09-427740 -
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 -
British Journal of Haematology May 2017Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic... (Review)
Review
Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A. Here, we present the current knowledge of clonal haematopoiesis in AA as it relates to aging, inherited bone marrow failure, and the grey-zone overlap of AA and myelodysplastic syndrome (MDS). We conclude by discussing the significance of clonal haematopoiesis both for improved diagnosis of AA, as well as for a more precise, personalized approach to prognostication of outcomes and therapy choices.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Child, Preschool; Clone Cells; Diagnosis, Differential; Female; Genetic Markers; Hematopoiesis; Hemoglobinuria, Paroxysmal; Humans; Immune Evasion; Infant; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Prognosis; Recurrence; Young Adult
PubMed: 28107566
DOI: 10.1111/bjh.14510 -
Pediatric Clinics of North America Dec 2013Molecular pathogenesis may be elucidated for inherited bone marrow failure syndromes (IBMFS). The study and presentation of the details of their molecular biology and... (Review)
Review
Molecular pathogenesis may be elucidated for inherited bone marrow failure syndromes (IBMFS). The study and presentation of the details of their molecular biology and biochemistry is warranted for appropriate diagnosis and management of afflicted patients and to identify the physiology of the normal hematopoiesis and mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies, which include ribosome assembly and ribosomal RNA processing. The Fanconi anemia pathway has become interdigitated with the familial breast cancer syndromes. In this article, the diseases that account for most IBMFS diagnoses are analyzed.
Topics: Anemia, Aplastic; Bone Marrow; Bone Marrow Diseases; Bone Marrow Failure Disorders; Hemoglobinuria, Paroxysmal; Humans; Ribosomes
PubMed: 24237972
DOI: 10.1016/j.pcl.2013.09.007 -
Hematology. American Society of... Dec 2017Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other... (Review)
Review
Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outcomes for aplastic anemia, acute myeloid leukemia, and MDS in patients with an IBMFS vs those occurring sporadically, as well as nonhematologic comorbidities in patients with IBMFSs, it is critical for hematologists to understand how to approach screening for the currently known IBMFSs. This review presents a practical approach for the clinical hematologist that outlines when to suspect an IBMFS and how to use various diagnostic tools, from physical examination to screening laboratory tests and genomics, for the diagnosis of the most frequent IBMFSs: Fanconi anemia, telomere biology disorders, Diamond-Blackfan anemia, GATA2 deficiency syndrome, Shwachman-Diamond syndrome, and severe congenital neutropenia.
Topics: Bone Marrow Diseases; Genetic Diseases, Inborn; Genetic Testing; Humans; Syndrome
PubMed: 29222240
DOI: 10.1182/asheducation-2017.1.79 -
Reumatismo Jul 2014Bone marrow edema (BME) is a descriptive term which identifies a specific magnetic resonance imaging (MRI) pattern that can be observed in a number of clinical entities,... (Review)
Review
Bone marrow edema (BME) is a descriptive term which identifies a specific magnetic resonance imaging (MRI) pattern that can be observed in a number of clinical entities, which are often characterized by pain as their main symptom, but show significant differences in terms of histopathological findings, causal mechanisms and prognosis. Bone marrow lesions in the subchondral bone of subjects with knee osteoarthritis (OA) seem to be associated with pain and progression of cartilage damage over time. Some histopathological studies of advanced OA have shown a prevalent fibrosis and bone marrow necrosis. BME of the subchondral bone in rheumatoid arthritis is associated with an infiltrate of inflammatory cells and osteoclasts and has a predictive value of further development of erosions. In spondyloarthritis, BME of the sacroiliac joints identifies an active sacroiliitis and is associated with histological inflammation and radiographic progression, whereas the relationship between BME lesions of the spine and syndesmophyte development is still controversial. BME syndromes (BMES), such as transient osteoporosis of the hip, regional migratory osteoporosis, and transient post-traumatic BMES, are characterized by a BME pattern on MRI and a self-limiting course. The potential evolution of BMES toward osteonecrosis is still controversial.
Topics: Arthritis, Rheumatoid; Bone Marrow Diseases; Edema; Humans; Magnetic Resonance Imaging; Osteoarthritis; Spondylarthritis; Syndrome
PubMed: 25069499
DOI: 10.4081/reumatismo.2014.790