Natural History of Paroxysmal Nocturnal Hemoglobinuria

Hillmen, Peter; Lewis, S. M.; Bessler, Monica; Luzzatto, Lucio; Dacie, J. V.

doi:10.1056/nejm199511093331904

Cited by 780 publications

(780 citation statements)

References 33 publications

Supporting

Mentioning

729

Contrasting

Unclassified

Order By: Relevance

“…This finding is consonant with the persistence of lymphocytes deficient in GPI-linked proteins in patients with long-term spontaneous remission of PNH (36), and it suggests that in a normal environment as well as in patients who are in remission, the negative selection to which PNH red cells and granulocytes succumb does not similarly affect PNH lymphocytes. In fact, in chimeric mice obtained after injection of pig-aϪ ES cells into rag-1Ϫ blastocysts, lymphopoiesis is rescued and supported for a lifetime by PNH lymphocytes (V. Rosti, unpublished observation).…”

Section: Pig-aϫ Es Cells Contribute In Vivo To Erythro-myelo-and Lympmentioning

confidence: 58%

Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion.

Rosti¹,

Tremml²,

Soares³

et al. 1997

J. Clin. Invest.

131

View full text Add to dashboard Cite

Paroxysmal nocturnal hemoglobinuria (PNH) develops in patients who have had a somatic mutation in the X-linked PIG-A gene in a hematopoietic stem cell; as a result, a proportion of blood cells are deficient in all glycosyl phosphatidylinositol (GPI)-anchored proteins. Although the PIG-A mutation explains the phenotype of PNH cells, the mechanism enabling the PNH stem cell to expand is not clear. To examine this growth behavior, and to investigate the role of GPI-linked proteins in hematopoietic differentiation, we have inactivated the pig-a gene by homologous recombination in mouse embryonic stem (ES) cells. In mouse chimeras, pig-a Ϫ ES cells were able to contribute to hematopoiesis and to differentiate into mature red cells, granulocytes, and lymphocytes with the PNH phenotype. The proportion of PNH red cells was substantial in the fetus, but decreased rapidly after birth. Likewise, PNH granulocytes could only be demonstrated in the young mouse. In contrast, the percentage of lymphocytes deficient in GPI-linked proteins was more stable. In vitro, pig-a Ϫ ES cells were able to form pig-a Ϫ embryoid bodies and to undergo hematopoietic (erythroid and myeloid) differentiation. The number and the percentage of pig-a Ϫ embryoid bodies with hematopoietic differentiation, however, were significantly lower when compared with wild-type embryoid bodies. Our findings demonstrate that murine ES cells with a nonfunctional pig-a gene are competent for hematopoiesis, and give rise to blood cells with the PNH phenotype. pig-a inactivation on its own, however, does not confer a proliferative advantage to the hematopoietic stem cell. This provides direct evidence for the notion that some additional factor(s) are needed for the expansion of the mutant clone in patients with PNH. ( J.

show abstract

Section: Pig-aϫ Es Cells Contribute In Vivo To Erythro-myelo-and Lympmentioning

confidence: 58%

Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion.

Rosti¹,

Tremml²,

Soares³

et al. 1997

J. Clin. Invest.

131

View full text Add to dashboard Cite

show abstract

“…The absence of complement control proteins, such as CD55 (decay accelerating factor) and CD59 (membrane inhibitor of reactive lysis), results in intravascular hemolysis. The clinical manifestations are characterized by a triad of intravascular hemolysis, venous thrombosis, and cytopenias (1). Such cytopenia is caused by bone marrow failure, and some patients may present with aplastic anemia (AA).…”

Section: Introductionmentioning

confidence: 99%

Successful Management of Obstructive Jaundice due to Gallstones with Eculizumab in a Patient with Paroxysmal Nocturnal Hemoglobinuria

et al. 2012

View full text Add to dashboard Cite

Paroxysmal nocturnal hemoglobinuria (PNH) makes patients susceptible to intravascular hemolysis and thrombosis, and it can be life-threatening in stressful situations. Eculizumab, a humanized monoclonal antibody that inhibits the complement protein C5, has been evaluated as a novel therapy for PNH. We herein describe the case of a 59-year-old Japanese woman with classic PNH, who had been successfully treated with eculizumab, but who later developed acute cholecystitis/cholangitis from gallstones. Although the severe obstructive jaundice requiring endoscopic therapy following cholecystectomy was complicated, critical intravascular hemolysis and thrombosis were not observed. Therefore, utilizing eculizumab during the peri-operative management of PNH patients should be carefully taken into consideration.

show abstract

“…It remains to be defined (a membrane inhibitor of reactive lysis or MIRL) on CD34 + PBSC from three PNH patients (one male and two females, whether this reflects different proportions of non-clonal residual hematopoiesis, a fact that could have prognostic sig-20-44 years old), mobilized by in vivo administration of G-CSF (Neupogen, Dompé-Biotec, or Granulokine, Roche, nificance for the heterogeneous population of PNH patients. 10 In the clinical setting, the combination of leukapheresis 9 Milan, Italy; 300 g/day s.c. for 5 days). CD59 was selected from among various other GPI-linked molecules, since it was and administration of G-CSF could be a feasible approach to achieving a larger number of CD34 + PBSC in PNH patients.…”

Section: Paroxysmal Nocturnal Hemoglobinuria (Pnh) Is An Acquiredmentioning

confidence: 99%

“…Because HLA has no primary role in the etiology of these diseases, a certain not accelerate the development of leukemia. It has to be noted that H-2 k and HLA-DR53 are serologically cross-reactive, 10 HLA genotype may be 'associated' with more than one disease. This is not speculation but a simple fact repeatedly shown in different studies.…”

Section: Paroxysmal Nocturnal Hemoglobinuria (Pnh) Is An Acquiredmentioning

confidence: 99%

Normal G-CSF-mobilized CD34+ peripheral blood stem cells in paroxysmal nocturnal hemoglobinia: a perspective for autologous transplantation

et al. 1997

View full text Add to dashboard Cite

Natural History of Paroxysmal Nocturnal Hemoglobinuria

Cited by 780 publications

References 33 publications

Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion.

Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion.

Successful Management of Obstructive Jaundice due to Gallstones with Eculizumab in a Patient with Paroxysmal Nocturnal Hemoglobinuria

Normal G-CSF-mobilized CD34+ peripheral blood stem cells in paroxysmal nocturnal hemoglobinia: a perspective for autologous transplantation

Contact Info

Product

Resources

About