Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platinum is the key drug in current treatment of ovarian cancer. The overall survival rate of patients with advanced ovarian cancer has improved. Recently, therapy-related myelodysplastic syndrome(T-MDS)and therapy-related leukemia( TRL)have been reported with increasing frequency in the literature. In this paper, we report two cases of TMDS followed by TRL after chemotherapy(TC therapy consisting of carboplatin and paclitaxel)with ovarian cancer stageIIIc. The interval from the primary chemotherapy to TMDS was 23 months or 90 months. The abnormal karyotype was observed in chromosomal analysis. Neither cases were given chemotherapy for TMDS, and died of the immunodeficiency. TRL and T-MDS are the most serious complications of chemotherapy. If pancytopenia is detected, bone marrow and cytogenetic examinations should be performed to rule out TMDS.
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PMID:[Secondary myelodysplasia and leukemia following carboplatin and paclitaxel-containing chemotherapy for ovarian cancer]. 1893 92

Peripheral blood cytopenia such as anemia, leukopenia with neutropenia and thrombocytopenia is frequently observed in cats infected with feline immunodeficiency virus (FIV). Although previous studies report that cytopenia has been observed in FIV-infected symptomatic cats, yet the asymptomatic cats also present cytopenia occasionally. In the present study, hematological and virological analyses in FIV-infected asymptomatic cats were carried out to understand the prevalence and pathogenesis of peripheral blood cytopenia in FIV infection. Hematological abnormalities were detected in 24 of 50 FIV-infected asymptomatic cats (48%) in which no other cause of cytopenia than FIV infection was observed. Anemia only, neutropenia only, thrombocytopenia only, bicytopenia and pancytopenia were observed in 10%, 10%, 6%, 14% and 8%, respectively. Bone marrow (BM) examination was performed in 8 FIV-infected asymptomatic cats with peripheral blood cytopenia. Myeloid dysplasia was observed in 4 cats with neutropenia of which 2 cats with concurrent thrombocytopenia presented morphological abnormalities of megakaryocytes. FIV-infected BM cells in the 8 cats were analyzed by PCR and immunocytochemistry. Lobulated mononuclear cells in BM were infected with FIV in 5 cats with neutropenia of which 2 cats with concurrent thrombocytopenia showed FIV-infected megakaryocytes. Parts of isolated stromal cells from BM were infected with FIV in all the 8 cats. Present results suggest that FIV infection of BM cells can cause peripheral blood cytopenia and myelodysplasia even if the cat is asymptomatic. Such FIV-related hematological abnormalities are supposed to be diagnosed as FIV-myelopathy.
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PMID:Prevalence of hematological abnormalities and detection of infected bone marrow cells in asymptomatic cats with feline immunodeficiency virus infection. 1911 Mar 84

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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PMID:Stem cell transplantation; Iranian experience. 1911 Oct 33

Secondary thrombocytopenia may result from autoimmune diseases, lymphoproliferative disorders, infections, myelodysplastic syndromes, common variable immunodeficiency, agammaglobulinemia, hypogammaglobulinemia, immunoglobulin A deficiency, and drugs. The presence of thrombocytopenia may result from chronic infections with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori and should be considered in the differential diagnosis of immune thrombocytopenic purpura (ITP). Studies have shown that upon diagnosis of infections, treatment of the primary disease allows for stabilization of platelet counts. Antiviral therapy with highly active antiretroviral therapy (HAART) for HIV has aided in platelet recovery with a corresponding decrease in circulating viral load. In some cases, the use of a thrombopoietin (TPO) agonist, eltrombopag, normalizes platelet levels in patients with these infections. Thrombocytopenia in the absence of other disease symptoms requires screening for H pylori, especially in regions where there is a high prevalence of the disease, such as in Japan, and in cases where platelets have normalized following eradication therapy. In other regions where these infections are not prevalent, such testing is controversial.
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PMID:Therapeutic strategies for hepatitis- and other infection-related immune thrombocytopenias. 1924 29

Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.
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PMID:Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. 2013 68

To gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathways. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or -7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with -7/del(7q) by pathways involved in cell survival, whereas patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder, thereby providing new targets for therapeutic intervention.
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PMID:Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells. 2022 Jul 79

Artemis is required for V(D)J recombination and the repair of a subset of radiation-induced DNA double strand breaks (DSBs). Artemis-null patients display radiosensitivity (RS) and severe combined immunodeficiency (SCID), classified as RS-SCID. Strongly impacting hypomorphic Artemis mutations confer marked infant immunodeficiency and a predisposition for EBV-associated lymphomas. Here, we provide evidence that a polymorphic Artemis variant (c.512C > G: p.171P > R), which has a world-wide prevalence of 15%, is functionally impacting. The c.512C > G mutation causes an approximately 3-fold decrease in Artemis endonuclease activity in vitro. Cells derived from a patient who expressed a single Artemis allele with the polymorphic mutational change, showed radiosensitivity and a DSB repair defect in G2 phase, with Artemis cDNA expression rescuing both phenotypes. The c.512C > G change has an additive impact on Artemis function when combined with a novel C-terminal truncating mutation (p.436C > X), which also partially inactivates Artemis activity. Collectively, our findings provide strong evidence that monoallelic expression of the c.512C > G variant impairs Artemis function causing significant radiosensitivity and a G2 phase DSB repair defect. The patient exhibiting monoallelic c.512C > G-Artemis expression showed immunodeficiency only in adulthood, developed bilateral carcinoma of the nipple and myelodysplasia raising the possibility that modestly decreased Artemis function can impact clinically.
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PMID:An Artemis polymorphic variant reduces Artemis activity and confers cellular radiosensitivity. 2103 Mar 22

An important indication for bone marrow investigation is the presence of bone marrow failure, which manifests itself as (pan)cytopenia. The causes of cytopenia are varied and differ considerably between childhood and adulthood. In the paediatric age group inherited bone marrow failure syndromes are important causes of bone marrow failure, but they play only a minor role in later life. This review gives a comprehensive overview of bone marrow failure disorders in children and adults. We classified the causes of bone marrow failure according to the main presenting haematological abnormality, i.e. anaemia, neutropenia, thrombocytopenia or pancytopenia. The following red cell disorders are discussed: red cell aplasia, sideroblastic anaemia, congenital dyserythropoietic anaemia, haemolytic anaemia, paroxysmal nocturnal haemoglobinuria, iron deficiency anaemia, anaemia of chronic disease and megaloblastic anaemia. The neutropenias occur in the context of Shwachman-Diamond syndrome (SDS), severe congenital neutropenia, cyclic neutropenia, immune-related neutropenia and non-immune neutropenia. In addition, the following causes of thrombocytopenia are discussed: congenital amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, immune-related thrombocytopenia and non-immune thrombocytopenia. Finally, we pay attention to the following pancytopenic disorders: Fanconi anaemia, dyskeratosis congenita, aplastic anaemia, myelodysplastic syndromes and human immunodeficiency virus (HIV) infection.
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PMID:The pathology of bone marrow failure. 2072 24

Four reports have been published on an association between acute myeloid leukaemia (AML) and primary lymphedema, with or without congenital deafness. We report seven new cases, including one extended family, confirming this entity as a genetic syndrome. The lymphedema typically presents in one or both lower limbs, before the hematological abnormalities, with onset between infancy and puberty and frequently affecting the genitalia. The AML is often preceded by pancytopenia or myelodysplasia with a high incidence of monosomy 7 in the bone marrow (five propositi and two relatives). Associated anomalies included hypotelorism, epicanthic folds, long tapering fingers and/or neck webbing (four patients), recurrent cellulitis in the affected limb (four patients), generalized warts (two patients), and congenital, high frequency sensorineural deafness (one patient). Children with lower limb and genital lymphedema should be screened for hematological abnormalities and immunodeficiency.
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PMID:Emberger syndrome-primary lymphedema with myelodysplasia: report of seven new cases. 2080 46

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive primary immunodeficiency characterised by immune dysregulation, microthrombocytopaenia, eczema and lymphoid malignancies. Mutations in the WAS gene can lead to distinct syndrome variations which largely, although not exclusively, depend upon the mutation. Premature termination and deletions abrogate Wiskott-Aldrich syndrome protein (WASp) expression and lead to severe disease (WAS). Missense mutations usually result in reduced protein expression and the phenotypically milder X-linked thrombocytopenia (XLT) or attenuated WAS [1-3]. More recently however novel activating mutations have been described that give rise to X-linked neutropenia (XLN), a third syndrome defined by neutropenia with variable myelodysplasia [4-6]. WASP is key in transducing signals from the cell surface to the actin cytoskeleton, and a lack of WASp results in cytoskeletal defects that compromise multiple aspects of normal cellular activity including proliferation, phagocytosis, immune synapse formation, adhesion and directed migration.
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PMID:The Wiskott-Aldrich syndrome: The actin cytoskeleton and immune cell function. 2117 75


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