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)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder resulting from a somatic mutation in the hematopoietic stem cell. It is characterized by intravascular hemolysis, cytopenias, frequent infections, bone marrow hypoplasia, and a high incidence of life-threatening venous thrombosis. An absent glycosylphosphatidylinositol (GPI)-anchored receptor prevents several proteins from binding to the erythrocyte membrane. These include the complement-regulatory proteins, CD55 and CD59, whose absence results in enhanced complement-mediated lysis. Patients present with anemia and hemoglobinuria. Laboratory diagnosis includes the sucrose hemolysis test, Ham acid hemolysis test, and fluorescent-activated cell analysis. There is considerable overlap between PNH, aplastic anemia, and myelodysplastic syndrome and some cases evolve into acute leukemia. Treatment is mainly supportive consisting of transfusion therapy, anticoagulation, and antibiotic therapy. Hematopoietic stem cell transplantation may be curative.
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PMID:Paroxysmal nocturnal hemoglobinuria. 1531 92

Although increased blood cell deficiency of glycosyl phosphatidylinositol-anchored membrane proteins has often been detected in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), the clinical significance of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells remains to be elucidated. We established a sensitive flow cytometric assay capable of detecting less than 0.01% of CD59-CD55- blood cells in a sample and used the assay to examine a large number of patients with bone marrow failure. An increase in the proportion of PNH-type cells was detectable in approximately 60% of all AA patients and in 20% of all refractory anemia (RA)-MDS patients. The increase was undetectable in patients with RA with an excessive number of blasts, acute myelogenous leukemia, multiple myeloma, or systemic lupus erythematosus. Our study showed that the presence of an increased number of PNH-type cells was predictive of a good response to immunosuppressive therapy and a favorable prognosis among patients with recently diagnosed AA and RA. A sensitive flow cytometric analysis for detection of a small population of PNH-type cells in peripheral blood cells is one of the most important examinations in the management of bone marrow failure.
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PMID:Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure. 1692 32

Coagulation abnormalities are frequently reported in hemolytic anemias (HA). Several pathophysiologic mechanisms are common to different HA. In this review three different hemolytic disorders will be discussed. In sickle cell disease and in beta-thalassemia, a thrombophilic status has been well documented as multifactorial involving hemostatic changes and activation of the coagulation cascade. Moreover, in such disorders, elevated levels of endothelial adhesion protein (ICAM-1, ELAM-1, VCAM-1, von Willebrand factor, and thrombomodulin) are often increased, suggesting that endothelial activation may be involved in vascular occlusion. As an additional mechanism of hypercoagulability in thalassemia, a procoagulant status of thalassemic red cells was recognized. The main clinical manifestation of paroxysmal nocturnal hemoglobinuria (PNH) is HA, and the most common complications are thrombosis, pancytopenia, and myelodysplastic syndrome or acute leukemia. The intravascular hemolysis is explained by a deficiency of glycosil phosphatidylinositol (GPI)-anchored complement regulatory proteins such as CD59 and CD55 on the membrane of red blood cells (RBCs), but the mechanism responsible for the increased incidence of thrombotic events in PNH remains unclear. Recent advances have been made in understanding the coagulation involvement in a heterogeneous group of diseases, thrombotic microangiopathies (TMA) characterized by microangiopathic hemolytic anemia and thrombocytopenia due to platelet clumping in the microcirculation, leading to ischemic organ dysfunction with neurologic symptoms and renal impairment.
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PMID:Coagulation in the pathophysiology of hemolytic anemias. 1802 12

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by absence of CD55 and CD59 from the surface of affected cells. PNH has been associated with myelodysplastic syndromes (MDS). The aim of our study was to estimate the prevalence of the PNH clone in MDS patients by detecting CD55 and CD59 deficiency. We studied 90 MDS patients: 19 patients with RA, 15 with refractory anemia with ringed sideroblasts (RARS), 18 with refractory anemia with excess of blasts (RAEB), 17 with refractory anemia with excess of blasts in transformation (RAEB-t), and 21 with chronic myelomonocytic leukemia (CMML). Twenty healthy individuals were also studied as the control group. We studied the PNH clone on granulocytes of these patients with the aid of flow cytometry. CD55- and CD59-deficient granulocytic populations were detected in 15.5% of MDS patients compared to 2.8% of normal individuals. Among the subgroups of the study, significant difference was present in three cases: (1) between CMML and control, (2) between CMML and RA, and (3) between CMML and RARS. These data indicate a possible association between PNH phenotype and MDS. MDS patients of worse prognosis (CMML) express more strongly the PNH clone compared to those of better prognosis (RA and RARS). Perhaps, the examination of MDS patients for the PNH clone by flow cytometry could provide us with a valuable prognostic tool.
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PMID:Detection of CD55- and CD59-deficient granulocytic populations in patients with myelodysplastic syndrome. 1815 79

Peripheral blood from 489 recently diagnosed patients with aplastic anaemia (AA) and 316 with refractory anaemia (RA) of myelodysplastic syndrome was evaluated to characterize CD55(-)CD59(-) [paroxysmal nocturnal haemoglobinuria (PNH)]-type blood cells associated with bone marrow (BM) failure. PNH-type cells were detected in 57% and 20% of patients with AA and RA, respectively. The percentages of PNH-type granulocytes ranged from 0.003% to 94.2% and the distribution was log-normal with a median of 0.178%. Serial analyses of 75 patients with PNH-type cells over 5 years revealed that the percentage of PNH-type cells constantly increased in 13 (17%), persisted in 44 (59%), disappeared in the remaining 18 (24%) although even in the 'Disappearance' group, PNH-type granulocytes persisted for at least 6 months. A scattergram profile of PNH-type cells unique to each patient persisted regardless of the response to immunosuppressive therapy and only single PIGA mutations were detected in PNH-type granulocytes sorted from four patients. These findings suggest that the PNH-type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self-maintenance properties of the individual PIGA mutants.
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PMID:Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure. 1965 54

Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) with flow cytometry traditionally involves the analysis of CD55 and CD59 on RBCs and neutrophils. However, the ability to accurately detect PNH RBCs is compromised by prior hemolysis and/or transfused RBCs. Patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS) can also produce PNH clones. We recently described a multiparameter fluorescent aerolysin (FLAER)-based flow assay using CD45, CD33, and CD14 that accurately identified PNH monocyte and neutrophil clones in PNH, AA, and MDS. Here, we compared the efficiency of this WBC assay with a CD59-based assay on RBCs during a 3-year period. PNH clones were detected with the FLAER assay in 63 (11.8%) of 536 samples tested, whereas PNH RBCs were detected in only 33 (6.2%), and always with a smaller clone size. The FLAER assay on WBCs is a more sensitive and robust primary screening assay for detecting PNH clones in clinical samples.
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PMID:Use of a FLAER-based WBC assay in the primary screening of PNH clones. 1976 34

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder, an acquired chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, recurrent infections, neutropenia, thrombocytopenia, and episodes of venous thrombosis. Its clinical course is highly variable. It frequently arises in association with bone marrow failure, particularly aplastic anemia and myelodysplastic syndrome. It is also an acquired thrombophilia, presenting with a variety of venous thrombosis, mainly manifested with intra-abdominal thrombosis, here the major cause of mortality. The triad of hemolytic anemia, pancytopenia, and thrombosis makes a truly unique clinical syndrome of PNH, which was reclassified from a purely acquired hemolytic anemia to a hematopoietic stem cell mutation defect of the phosphatidyl inositol glycanclass-A gene. This mutation results in an early block in the synthesis of glycosylphosphatidylinositol (GPI) anchors, responsible for binding membrane functional proteins. Among these proteins are the complement inhibitors, especially CD55 and CD59, that play a key role in protecting blood cells from complement cascade attack. Therefore, in PNH occurs an increased susceptibility of red cells to complement, and consequently, hemolysis. We here review PNH physiopathology, clinical course, and treatment options, especially eculizumab, a humanized monoclonal antibody that blocks the activation of terminal complement at C5 and prevents formation of the terminal complement complex, the first effective drug therapy for PNH.
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PMID:[Paroxysmal nocturnal hemoglobinuria: from physiopathology to treatment]. 2049 98

Paroxysmal nocturnal hemoglobinuria is caused by expansion of a hematopoietic stem cell clone with an acquired somatic mutation in the PIG-A gene. This mutation aborts the synthesis and expression of the glycosylphosphatidylinositol anchor proteins CD55 and CD59 on the surface of blood cells, thereby making them more susceptible to complement-mediated damage. A spectrum of disorders occurs in PNH ranging from hemolytic anemia and thrombosis to myelodysplasia, aplastic anemia and, myeloid leukemias. Aplastic anemia is one of the most serious and life-threatening complications of PNH, and a PNH clone is found in almost a third of the cases of aplastic anemia. While allogeneic bone marrow transplantation and T cell immune suppression are effective treatments for aplastic anemia in PNH, these therapies have significant limitations. We report here the first case, to our knowledge, of PNH associated with aplastic anemia treated with the anti-CD20 monoclonal antibody rituximab, which was associated with a significant reduction in the size of the PNH clone and recovery of hematopoiesis. We suggest that this less toxic therapy may have a significant role to play in treatment of PNH associated with aplastic anemia.
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PMID:Response of paroxysmal nocturnal hemoglobinuria clone with aplastic anemia to rituximab. 2293 17

A normal karyotype is usually present in cases of classic paroxysmal nocturnal hemoglobinuria (PNH), whereas chromosomal abnormalities involving chromosome bands 13q12 to 13q14 (13q12q14) are frequently found in various hematologic malignancies, including chronic lymphoblastic leukemia (CLL) and myelodysplastic syndrome (MDS). Here, we present a case of a 55-year-old male patient with PNH who had a deletion of chromosome 13q [del(13q)]. He presented with cough, fever, and pancytopenia. Flow cytometry of the patient's peripheral blood demonstrated that 21.7% and 21.5% of the erythrocytes were CD59 and CD55 deficient, respectively, and 63.5% of the granulocytes were FLAER and CD24 deficient. Examination of the bone marrow indicated that blasts were not increased but mild dyshematopoietic features were present. Conventional cytogenetic analysis and fluorescence in situ hybridization revealed a deletion of chromosome 13q (q12q14). The patient received an allogeneic hematopoietic stem cell transplantation. Whether this abnormality can be considered as an evidence of MDS in the setting of overt PNH requires an evaluation in the future.
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PMID:Paroxysmal nocturnal hemoglobinuria with deletion of chromosome 13q (q12q14): a case report and review of the literature. 2296 21

Myelodysplastic syndrome (MDS) comprises a group of stem cell disorders with considerable clinical and morphological heterogeneity. We report a case of MDS in a middle-aged male with clinical features of sepsis, dysplastic neutrophils and 6% blasts on bone marrow aspirate. A clone of neutrophils with deficient expression of CD16, CD55 and CD59 was found. A diagnosis of MDS with excess blasts with co-existent paroxysmal nocturnal hemoglobinuria (PNH) was made. Within a fortnight, the patient progressed to acute myeloid leukemia. We are reporting this unusual case of MDS displaying a sizeable clone of dysplastic neutrophils deficient in glycosyl phosphatidyl inositol anchored proteins, highlighting a common origin of PNH and leukemic clone.
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PMID:Paroxysmal nocturnal hemoglobinuria clone in a case of myelodysplastic syndrome rapidly progressing to acute leukemia. 2310 Sep 70


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