Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody.

Rosse, Wendell F.; Dacie, J. V.

doi:10.1172/jci105388

Cited by 278 publications

(140 citation statements)

References 21 publications

(27 reference statements)

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“…8 Nevertheless, how a single mutation can contribute to the pathogenesis of three phenotypically distinct disease entities is still largely unclear. One study, using a JAK2-V617F transgenic mouse model, suggested that the disease phenotype could be determined by the ratio of mutant JAK2 to wild-type protein.…”

Section: Molecular Basis and Clonal Evolution Of Myeloproliferative Nmentioning

confidence: 99%

“…Observations of strain-specific differences in JAK2-V617F-associated disease phenotypes between Balb/c and C57Bl/6 mice suggest an involvement of germ line features in the resultant phenotype. 8 However, besides JAK2 mutations and other oncogenic events targeting the JAK-STAT pathway (such as mutations in the MPL gene, coding for the thrombopoietin receptor and truncations of the erythropoietin receptor), 8 there are still many uncharacterized somatic cytogenetic lesions present within the MPN clone, harboring a series of candidates for both the induction of clonal expansion and the MPN phenotype decision.…”

Section: Molecular Basis and Clonal Evolution Of Myeloproliferative Nmentioning

confidence: 99%

“…4 The last qualification is not trivial, because even today the accesses of hemoglobinuria, most distressing for the patient, may tend to obscure the fact that in PNH hemolysis goes on all the time: macroscopic hemoglobinuria merely reflects its exacerbations. 5 That in PNH hemolysis was complement-dependent has also been known for a long time ( Figure 1): indeed, the acidified serum (or Ham-Dacie) test, based on complement-mediated lysis of PNH cells in vitro, has for half a century been the gold standard for the diagnosis of PNH, 7,8 until flow cytometry came into its own. 9,10 Therefore stopping hemolysis by blocking complement was a logical idea: it did not seem easy to achieve this safely in vivo.…”

mentioning

confidence: 98%

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Paroxysmal nocturnal hemoglobinuria and eculizumab

Luzzatto¹,

Risitano²,

Notaro³

2010

Haematologica

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Section: Molecular Basis and Clonal Evolution Of Myeloproliferative Nmentioning

confidence: 99%

Section: Molecular Basis and Clonal Evolution Of Myeloproliferative Nmentioning

confidence: 99%

mentioning

confidence: 98%

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Paroxysmal nocturnal hemoglobinuria and eculizumab

Luzzatto¹,

Risitano²,

Notaro³

2010

Haematologica

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“…In virtually all patients, blood cells with the PNH phenotype coexist with phenotypically normal blood cells. The severity of the clinical picture correlates broadly with the size of the PNH clone and with the degree of deficiency in GPIlinked proteins; specifically, the intensity of the hemolysis reflects the number of red cells deficient in CD59 and CD55, and the degree of deficiency in these two proteins (11).…”

Section: Introductionmentioning

confidence: 99%

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

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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.

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“…PNH is an acquired disorder, characterized by chronic intravascular hemolysis resulting from an increased sensitivity of erythrocytes to activated complements [17]. Absence of red cell surfaces of complement regulatory proteins such as CDS9 and decay-accelerating factor (DAF) is responsible for the hypersensitivity to complement of the red cells [18,19].…”

Section: Pnhmentioning

confidence: 99%

Hematopoietic progenitor cells in the blood and bone marrow in various hematologic disorders

et al. 2009

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Hematopoietic progenitor cells are present in the blood and the bone marrow. Changes in the numbers of hematopoietic progenitor cells reflect alteration of pluripotent stem cells. We discus such changes in common hematologic diseases including aplastic anemia, paroxysmal nocturnal hemoglobinnria (PNl3) and thalassemia, In aplastic anemia, the numbers of burst forming unitserythroid (BFU-E) and colony-forming units-granulwybmacrophage (Cmr-GM) are much decreased; the decrease stiU exists &r recovery from therapy. In PNH, the numbers of progenitor cells are low, even in the presence of marrow hypercellnlarity. In thalmmia, the numbers of progenitor cells are niuch increased; more pronounced in splenectomized patients. Stem Ceh 1998;16(~u~pl1):123-128

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Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody.

Cited by 278 publications

References 21 publications

Paroxysmal nocturnal hemoglobinuria and eculizumab

Paroxysmal nocturnal hemoglobinuria and eculizumab

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

Hematopoietic progenitor cells in the blood and bone marrow in various hematologic disorders

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