The Molecular Biology of Paroxysmal Nocturnal Hemoglobinuria (PNH)

2014-08-27 03:28:50 | BioPortfolio


This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic stem cell renewal.


Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, thrombosis, and variable cytopenia. It can be associated with significant morbidity including acute kidney failure, cerebral infarction, mesenteric infarction, Budd-Chiari syndrome, aplastic anemia, and leukemic transformation. The average survival time from diagnosis is 15 years.

PNH is an acquired clonal disorder of the hematopoietic stem cell. Two distinct populations of hematopoietic cells exist in each PNH patient: one non-clonal population of normal cells, and one clonal population of PNH cells. The clonal population of PNH cells is identified by a mutation in the PIG-A gene that results in absence of the glycophosphatidylinositol (GPI) anchor of several surface proteins. Consequently, these surface proteins are unable to perform their functions on the cell surface. Deficiency of two of these surface proteins, CD55 (decay accelerating factor) and CD59 (membrane inhibitor of reactive lysis) that prevent complement mediated destruction, have been shown to underlie the clinical presentation of PNH. Identifying the mutation causing the predominant clones may help us better understand the molecular biology of PNH. When this is accomplished, new therapies to control and eventually cure the disease can be designed.

In addition, we propose to determine the function of PrP in human hematopoietic stem cells. PrP is a glycoprotein attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. In PNH, a disorder whose pathogenesis lies in the absence of GPI anchors, PrP expression is reduced in monocytes and granulocytes from the PNH clone.

Study Design

Observational Model: Cohort, Time Perspective: Prospective


Hemoglobinuria, Paroxysmal


University of Utah
Salt Lake City
United States




University of Utah

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:28:50-0400

Clinical Trials [171 Associated Clinical Trials listed on BioPortfolio]

Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry

This study is a collection of data to evaluate safety and characterize progression of Paroxysmal Nocturnal Hemoglobinuria (PNH).

A Phase 3, Open-Label Study of ALXN1210 in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (PNH)

The purpose of this study is to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ALXN1210 in pediatric patients with paroxysmal nocturnal hemoglobinuria (PN...

Paroxysmal Nocturnal Hemoglobinuria in ESUS & ETUS

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Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria

The purpose of this study is to determine whether LFG316 can induce a hematological response, as measured by reduction in hemolytic activity, in patients with PNH.

A Treatment Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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PubMed Articles [103 Associated PubMed Articles listed on BioPortfolio]

Ecthyma Gangrenosum in Paroxysmal Nocturnal Hemoglobinuria.

Correction to: Effects of eculizumab treatment on quality of life in patients with paroxysmal nocturnal hemoglobinuria in Japan.

In the original publication of this article, Tables 2, 3 and 4 were published incorrectly. The corrected tables 2, 3 and 4 are given in the following pages.

How we treat paroxysmal nocturnal hemoglobinuria: a consensus statement of the Canadian PNH Network and review of the national registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by intravascular hemolysis, thrombophilia, and marrow failure. Its phenotype is due to absent or reduced expressio...

Evolutionary dynamics of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder characterized by hemolysis and a high risk of thrombosis, that is due to a deficiency in several cell surface proteins th...

Prothrombotic mechanisms in patients with congenital p.Cys89Tyr mutation in CD59.

Thrombosis is the prognostic factor with the greatest effect on survival in patients with paroxysmal nocturnal hemoglobinuria (PNH), who lack dozens of membrane surface proteins. We recently described...

Medical and Biotech [MESH] Definitions

A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.

A parasomnia characterized by paroxysmal episodes of choreoathetotic, ballistic, dystonic movements, and semipurposeful activity. The episodes occur during non-rapid eye movement sleep and typically recur several times per night. (Neurology 1992 Jul;42(7 Suppl 6):61-67; Adams et al., Principles of Neurology, 6th ed, p391)

The presence of free HEMOGLOBIN in the URINE, indicating hemolysis of ERYTHROCYTES within the vascular system. After saturating the hemoglobin-binding proteins (HAPTOGLOBINS), free hemoglobin begins to appear in the urine.

Abnormally rapid heartbeats with sudden onset and cessation.

A respiratory infection caused by BORDETELLA PERTUSSIS and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath.

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