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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelodysplastic syndrome (MDS) is a clonal blood disorder characterized by ineffective hematopoiesis, cytopenias, dysplasia and an increased risk of acute myeloid leukemia (AML). With the growing availability of clinical genetic testing, there is an increasing appreciation that a number of genetic predisposition syndromes may underlie apparent de novo presentations of MDS/AML, particularly in children and young adults. Recent findings of clonal hematopoiesis in acquired aplastic anemia add another facet to our understanding of the mechanisms of MDS/AML predisposition. As more predisposition syndromes are recognized, it is becoming increasingly important for hematologists and oncologists to have familiarity with the common as well as emerging syndromes, and to have a systematic approach to diagnosis and screening of at risk patient populations. Here, we provide a practical algorithm for approaching a patient with a suspected MDS/AML predisposition, and provide an in-depth review of the established and emerging familial MDS/AML syndromes caused by mutations in the ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes. Finally, we discuss recent data on the role of somatic mutations in malignant transformation in acquired aplastic anemia, and review the practical aspects of MDS/AML management in patients and families with predisposition syndromes.
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PMID:Genetic predisposition to myelodysplastic syndrome and acute myeloid leukemia in children and young adults. 2669 94

Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia.
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PMID:[Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia]. 2687 64

We report the identification of a new case of familial non syndromic severe thrombocytopenia. Bleeding was mild and no extra-haematological symptoms were found. Platelet morphology was normal as well as the quantitative expression of platelet membrane glycoproteins. Platelet functions could not be studied due to the intensity of the thrombocytopenia. Molecular analysis identified a mutation located in the promoter of the ankyrin repeat domain 26 (ANKRD26) gene, c.-127A>T, recently reported to be responsible of normocytic thrombocytopenia, but also of a possible increased risk of leukemia/myelodysplasia. Actual knowledge on this new type of inherited thrombocytopenia is also presented.
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PMID:ANKRD26 normocytic thrombocytopenia: a family report. 2710 25

Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SBS), hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA) and significantly increased risks for MDS and/or acute myeloid leukemia (AML) in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.
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PMID:Hereditary Predispositions to Myelodysplastic Syndrome. 2724 96

Although genetic predisposition to haematological malignancies has long been known, genetic testing is not yet the part of the routine diagnostics. In the last ten years, next generation sequencing based studies identified novel germline mutations in the background of familial aggregation of certain haematologic disorders including myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). This is supported by the fact that the myeloid neoplasms with genetic predisposition represent a new category in the revised 2016 World Health Organization classification. According to the new classification, these disorders are subdivided based on the clinical and genetic features, including myeloid neoplasms with germline predisposition alone, or with pre-existing platelet disorder, cytopaenias or other organ failures. The predisposing genetic factors include mutations in the RUNX1, CEBPA, GATA2, ANKRD26, ETV6, DDX41, TERC or TERT and SRP72 genes. The genes affected in these syndromes are important regulators of haemopoiesis and are frequently implicated in leukaemogenesis, providing deeper insight into the understanding of normal and malignant haemopoiesis. Despite the growing knowledge of germline predisposing events in the background of familial myeloid malignancies, the germline genetic component is still unknown in a subset of these pedigrees. Here, we present the first study of inherited myeloid malignancies in Hungary. We identified three families with apparent clustering of myeloid malignancies with nine affected individuals across these pedigrees. All tested individuals were negative for CEBPA, GATA2, RUNX1, ANKRD26, ETV6, DDX41, TERC or TERT and SRP72 mutations, suggesting the presence of so far unidentified predisposing mutations.
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PMID:Familial Acute Myeloid Leukemia and Myelodysplasia in Hungary. 2835 85

Patients with thrombocytopenia 5 have an autosomal dominant disorder of decreased platelet number with tendency to bleed, usually presenting in childhood, and have been found to have germline mutations in ETV6, which encodes a master hematopoietic transcription factor. Some patients who present similarly have inherited mutations in RUNX1 or ANKRD26. All three germline syndromes are also associated with a predisposition to myelodysplastic syndrome (MDS) and acute leukemia (AL). Since the first description of germline ETV6 mutations, 18 families have been reported. The common phenotype is mild to moderate thrombocytopenia with a variable predisposition to acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and MDS. This review will focus upon the role of ETV6 in hematopoiesis, especially in myeloid differentiation and maturation, and will describe the functional effects of mutant ETV6. The review will also provide an overview of common clinical features as well as recommendations for patient screening and follow-up and will debate whether additional clinical features should be included with the germline ETV6 syndrome.
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PMID:Germline ETV6 mutations and predisposition to hematological malignancies. 2855 14

Advances in molecular genetic sequencing techniques have contributed to the elucidation of previously unknown germline mutations responsible for inherited thrombocytopenia (IT). Regardless of age of presentation and severity of symptoms related to thrombocytopenia and/or platelet dysfunction, a subset of patients with IT are at increased risk of developing myeloid neoplasms during their life time, particularly those with germline autosomal dominant mutations in RUNX1, ANKRD26, and ETV6. Patients may present with isolated thrombocytopenia and megakaryocytic dysmorphia or atypia on baseline bone marrow evaluation, without constituting myelodysplasia (MDS). Bone marrow features may overlap with idiopathic thrombocytopenic purpura (ITP) or sporadic MDS leading to misdiagnosis. Progression to myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML) may be accompanied by progressive bi- or pancytopenia, multilineage dysplasia, increased blasts, cytogenetic abnormalities, acquisition of bi-allelic mutations in the underlying gene with germline mutation, or additional somatic mutations in genes associated with myeloid malignancy. A subset of patients may present with MDS/AML at a young age, underscoring the growing concern for evaluating young patients with MDS/AML for germline mutations predisposing to myeloid neoplasm. Early recognition of germline mutation and predisposition to myeloid malignancy permits appropriate treatment, adequate monitoring for disease progression, proper donor selection for hematopoietic stem cell transplantation, as well as genetic counseling of the affected patients and their family members. Herein, we describe the clinical and diagnostic features of IT with germline mutations predisposing to myeloid neoplasms focusing on mutations involving RUNX1, ANKRD26, and ETV6.
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PMID:Inherited thrombocytopenia and platelet disorders with germline predisposition to myeloid neoplasia. 3106 78

Myelodysplastic syndromes and acute myeloid leukemia are sporadic for the majority of cases affecting the elderly population. Inherited cases, however, do occur. Genetic predispositions to myeloid malignancies can be classified into three categories: familial cancer syndromes associated with increased risk of various malignancies including myelodysplasia and acute myeloid leukemia such as Li-Fraumeni syndrome and constitutional mismatch repair deficiency (CMMRD); germline mutations conferring a specific increased risk of myelodysplastic syndrome and acute myeloid leukemia such as mutations in ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes; and finally primarily pediatric inherited bone marrow failure syndromes such as Fanconi anemia, dyskeratosis congenita, severe congenital neutropenia, Shwachman-Diamond syndrome and Diamond Blackfan anemia. The recognition of these germline syndromes is essential in the management and follow-up of patients. Herein, we review the conditions associated with hereditary myeloid leukemia with a special clinical focus on management and monitoring.
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PMID:Hereditary myeloid malignancies. 3120 98

Ankyrin repeat domain-containing protein 26- (ANKRD26-) related thrombocytopenia is a rare, autosomal dominant condition caused by ANKRD26 gene mutation. ANKRD26-related thrombocytopenia is characterized by moderate thrombocytopenia with minimal bleeding, normal platelet size, and dysmegakaryopoiesis on bone marrow evaluation. ANKRD26 mutation has been previously associated with myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. We report the first case of multiple myeloma in a patient with ANKRD26 related thrombocytopenia. The patient was successfully treated with contemporary combination therapy followed by melphalan-conditioned autologous stem cell transplant for his multiple myeloma despite preexisting thrombocytopenia.
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PMID:Multiple Myeloma in a Patient with ANKRD26-Related Thrombocytopenia Successfully Treated with Combination Therapy and Autologous Stem Cell Transplant. 3128 87

Thrombocytopenia 2 (THC2) is an autosomal dominant disorder characterized by ankyrin repeat domain 26 mutation and moderate thrombocytopenia. THC2 exposes patients to a low risk of bleeding and an increased likelihood of myelodysplastic syndrome/acute myeloid leukemia. Germline evaluation for a genetic disorder should be considered when a patient presents with isolated thrombocytopenia and associated dysmegakaryopoiesis. In this case report, we present a male patient who presented with isolated thrombocytopenia but was ultimately confirmed to have an inherited THC2 thrombocytopenia/myelodysplastic syndrome. Given the rarity of the disease, no clear guidelines on how to follow THC2 patients over the long term have been established. We recommend a monthly complete blood count and clinical visits every 3 months at a minimum.
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PMID:Inherited Thrombocytopenia Caused by Germline ANKRD26 Mutation Should Be Considered in Young Patients With Suspected Myelodysplastic Syndrome. 3261 8


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