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

Clinical evidence for a link between aplastic anaemia, paroxysmal nocturnal haemoglobinuria (PNH) and hypoplastic leukaemia is provided by studies of clonal disorders, which may be a complication of congenital or acquired aplastic anaemia. Fanconi's anaemia is the most common congenital disorder and leukaemia occurs in at least 10% of cases. In acquired aplastic anaemia, a high incidence of myelodysplastic syndrome (MDS) was noted in patients with aplastic anaemia, seemingly cured of their aplasia by antilymphocyte globulins (ALG). In a recent survey, the 10-year cumulative incidence rates were 9.6% for MDS, 6.6% for acute leukaemia (115-fold higher than in the general population). Biological evidence is provided by bone marrow morphology, as a certain degree of dysmyelopoiesis is not unusual in aplastic anaemia. Cytogenetic analyses in aplastic anaemia are scarce, but data have shown clonal cytogenetic abnormalities at diagnosis in otherwise typical aplastic anaemia. Recently, flow cytometry to assess the glycosyl-phosphatidylinositol (GPI) molecule defect in PNH has demonstrated that a significant proportion of patients with otherwise typical aplastic anaemia have, in fact, a GPI defect due to alterations within the PIG-A gene. Finally, aplastic anaemia patients were recently reported to have molecular evidence of clonal haematopoiesis; this must now be discussed in light of recent clonality studies in normal individuals. The clinical and biological evidence for a link between aplastic anaemia, PNH and hypoplastic leukaemia allows the generation of a model of aplastic anaemia as a possible pre-pre-leukaemic disorder.
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PMID:Could aplastic anaemia be considered a pre-pre-leukaemic disorder? 898 43

The myelodysplastic syndromes (MDS) are a group of hematologic disorders commonly affecting elderly persons and often leading to acute myelogenous leukemia (AML). Although rare in children, when MDS does occur, it is frequently part of a congenital disorder such as Shwachman-Diamond syndrome (SDS). Monosomy 7 and/or deletion of part or all of 7q are poor prognostic signs in MDS and AML, although the pathophysiologic relationship between this finding and MDS or AML is unclear. Shwachman-Diamond syndrome is an inherited illness characterized by exocrine pancreatic insufficiency and by congenital neutropenia. Patients with SDS are at increased risk of developing myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Because monosomy 7 is a poor prognostic sign in MDS and AML, establishing its presence is important. However, different methods of detection of monosomy 7 may lead to different results in some patients. We present the case of a 10-year-old girl known to have SDS, who had a bone marrow aspiration and biopsy done to rule out MDS and AML. By light microscopy, the patient's bone marrow was unremarkable. GTG-banding showed the following karyotype: 45,XX,-C[3]/47,XX,+C[1]/46,XX[45]. Fluorescence in situ hybridization (FISH) was performed with a chromosome 7-specific alpha-satellite probe (D7Z1). Almost all (373 of 376) cells exhibited only one chromosome 7 signal. A second marrow aspiration done 6 months later showed an essentially normal karyotype by GTG-banding. Fluorescence in situ hybridization with the same chromosome 7 probe showed 230 of 250 cells to be monosomic for chromosome 7. A whole chromosome 7 painting probe demonstrated disomy for chromosome 7 in 90 of 90 cells; however, subtle heteromorphism in the centromeric regions of the 2 copies of chromosome 7 was noted in some cells. This case demonstrates that FISH and GTG-banding can give discordant results, that the two should be viewed as complementary technologies, and that both have a place in a full karyotypic analysis. Furthermore, this case demonstrates for the first time that heteromorphism and/or subtle structural abnormalities of chromosome 7, previously associated with MDS and AML, can exist without clinical or morphologic signs of these illnesses. It will be of interest to further study the relationship, if any, between SDS and various structural abnormalities of chromosome 7 in MDS and AML, and to elucidate the molecular mechanisms of pathogenesis, physiology, and treatment of these disorders.
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PMID:Discordant detection of monosomy 7 by GTG-banding and FISH in a patient with Shwachman-Diamond syndrome without evidence of myelodysplastic syndrome or acute myelogenous leukemia. 1059 42

Mitochondria are involved in hematopoietic cell homeostasis through multiple ways such as oxidative phosphorylation, various metabolic processes and the release of cytochrome c in the cytosol to trigger caspase activation and cell death. In erythroid cells, the mitochondrial steps in heme synthesis, iron (Fe) metabolism and Fe-sulfur (Fe-S) cluster biogenesis are of particular importance. Mutations in the specific delta-aminolevulinic acid synthase (ALAS) 2 isoform that catalyses the first and rate-limiting step in heme synthesis pathway in the mitochondrial matrix, lead to ineffective erythropoiesis that characterizes X-linked sideroblastic anemia (XLSA), the most common inherited sideroblastic anemia. Mutations in the adenosine triphosphate-binding cassette protein ABCB7, identified in XLSA with ataxia (XLSA-A), disrupt the maturation of cytosolic (Fe-S) clusters, leading to mitochondrial Fe accumulation. In addition, large deletions in mitochondrial DNA, whose integrity depends on a specific DNA polymerase, are the hallmark of Pearson's syndrome, a rare congenital disorder with sideroblastic anemia. In acquired myelodysplastic syndromes at early stage, exacerbation of physiological pathways involving caspases and the mitochondria in erythroid differentiation leads to abnormal activation of a mitochondria-mediated apoptotic cell death pathway. In contrast, oncogenesis-associated changes at the mitochondrial level can alter the apoptotic response of transformed hematopoietic cells to chemotherapeutic agents. Recent findings in mitochondria metabolism and functions open new perspectives in treating hematopoietic cell diseases, for example various compounds currently developed to trigger tumor cell death by directly targeting the mitochondria could prove efficient as either cytotoxic drugs or chemosensitizing agents in treating hematological malignancies.
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PMID:Mitochondria in hematopoiesis and hematological diseases. 1689 88

We report a rare case of myelodysplastic syndrome that presented early as amegakaryocytic thrombocytopenia in a collodion baby, which is a rare congenital disorder characterized by thick, taut membrane resembling oiled parchment or collodion, which is subsequently shed. To our knowledge, this is the first reported case of a collodion baby who presented with amegakaryocytic thrombocytopenia and who has a significant family history of the same condition. We document the rarity of this possible association and also the need for further study to establish whether a causal relationship exists.
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PMID:Myelodysplastic Syndrome Presenting as Amegakaryocytic Thrombocytopenia in a Collodion Baby. 2690 3

Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition.
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PMID:SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. 2718 67

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia. Of the three cases of AML found in TAR patient, only one was reported in an adult. We report a case of myelodysplastic syndrome progressing to AML with calreticulin driver mutation in an adult male with TAR syndrome who was successfully treated with hematopoietic allogeneic stem cell transplantation.
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PMID:Acute myeloid leukemia in a patient with thrombocytopenia with absent radii: A case report and review of the literature. 2825 46

Adrenal hypoplasia is a rare congenital disorder. In spite of biochemical and molecular genetic evaluation, etiology in many patients with adrenal hypoplasia is not clear. MIRAGE syndrome is a recently recognized congenital disorder characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Here we present a case of MIRAGE syndrome due to a heterozygous missense variant (c.2920G>A; p.E974K) mutation in the sterile alpha motif domain-containing protein-9 (SAMD9) gene. This report describes the first MIRAGE syndrome patient in Turkey.
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PMID:A Rare Etiology of 46,XY Disorder of Sex Development and Adrenal Insufficiency: A Case of MIRAGE Syndrome Caused by Mutations in the SAMD9 Gene 3120 61