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Leukemia Research Feb 2017Patients with acquired and inherited bone marrow failure syndromes (BMFS) have ineffective hematopoiesis due to impairments of the hematopoietic stem cell compartment.... (Review)
Review
Patients with acquired and inherited bone marrow failure syndromes (BMFS) have ineffective hematopoiesis due to impairments of the hematopoietic stem cell compartment. Common manifestations of BMFS include varying degrees of peripheral blood cytopenias and, sometimes, progression to acute myelogenous leukemia. Research efforts have been made all over the world to improve understanding of the pathogenesis of these diseases and their clinical implications. The Aplastic Anemia and MDS International Foundation (AAMDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize recent scientific discoveries in several BMFS that were presented at the fifth International Bone Marrow Failure Disease Scientific Symposium 2016 that AAMDSIF sponsored on March 17-18, 2016, in Rockville, Maryland.
Topics: Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Hematopoietic Stem Cells; Hemoglobinuria, Paroxysmal; Humans; Myelodysplastic Syndromes
PubMed: 27923195
DOI: 10.1016/j.leukres.2016.11.011 -
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 -
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 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 -
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 -
Blood Jan 2023Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and...
Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and immunosuppression are effective, but they entail costs and risks, and are not always successful. The Janus kinase (JAK) 1/2 inhibitor ruxolitinib (RUX) suppresses cytotoxic T-cell activation and inhibits cytokine production in models of graft-versus-host disease. We tested RUX in murine immune AA for potential therapeutic benefit. After infusion of lymph node (LN) cells mismatched at the major histocompatibility complex [C67BL/6 (B6)⇒CByB6F1], RUX, administered as a food additive (Rux-chow), attenuated bone marrow hypoplasia, ameliorated peripheral blood pancytopenia, preserved hematopoietic progenitors, and prevented mortality, when used either prophylactically or therapeutically. RUX suppressed the infiltration, proliferation, and activation of effector T cells in the bone marrow and mitigated Fas-mediated apoptotic destruction of target hematopoietic cells. Similar effects were obtained when Rux-chow was fed to C.B10 mice in a minor histocompatibility antigen mismatched (B6⇒C.B10) AA model. RUX only modestly suppressed lymphoid and erythroid hematopoiesis in normal and irradiated CByB6F1 mice. Our data support clinical trials of JAK/STAT inhibitors in human AA and other immune bone marrow failure syndromes.
Topics: Mice; Humans; Animals; Pancytopenia; Anemia, Aplastic; Bone Marrow Failure Disorders; Bone Marrow; Bone Marrow Diseases; Janus Kinase 1
PubMed: 36130301
DOI: 10.1182/blood.2022015898 -
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 -
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 -
British Journal of Haematology May 2017The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to... (Review)
Review
The inherited bone marrow failure syndromes (IBMFS) typically present with significant cytopenias in at least one haematopoietic cell lineage that may progress to pancytopenia, and are associated with increased risk of cancer. Although the clinical features of the IBMFS are often diagnostic, variable disease penetrance and expressivity may result in diagnostic dilemmas. The discovery of the genetic aetiology of the IBMFS has been greatly facilitated by next-generation sequencing methods. This has advanced understanding of the underlying biology of the IBMFS and been essential in improving clinical management and genetic counselling for affected patients. Herein we review the clinical features, underlying biology, and new genomic discoveries in the IBMFS, including Fanconi anaemia, dyskeratosis congenita, Diamond Blackfan anaemia, Shwachman Diamond syndrome and some disorders of the myeloid and megakaryocytic lineages.
Topics: Anemia, Aplastic; Anemia, Diamond-Blackfan; Blood Platelet Disorders; Bone Marrow Diseases; Bone Marrow Failure Disorders; DNA Repair-Deficiency Disorders; Dyskeratosis Congenita; Exocrine Pancreatic Insufficiency; Fanconi Anemia; Genetic Counseling; Genomics; Hemoglobinuria, Paroxysmal; Humans; Lipomatosis; Neutropenia; Ribosomes; Shwachman-Diamond Syndrome; Telomere
PubMed: 28211564
DOI: 10.1111/bjh.14535 -
European Journal of Nuclear Medicine... Jan 2011Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds... (Review)
Review
Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as (99m)Tc-nanocolloid, (99m)Tc-sulphur colloid, (111)In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using (18)F-FDG and (18)F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed.
Topics: Animals; Bone Marrow Diseases; Cell Proliferation; Humans; Radionuclide Imaging
PubMed: 20625724
DOI: 10.1007/s00259-010-1531-0