Paroxysmal Nocturnal Haemoglobinuria: Nature's Gene Therapy?

Overview

Journal Mol Pathol

Specialty Molecular Biology

Date 2002 May 29

PMID 12032224

Citations 5

Authors

R J Johnson

P Hillmen

Affiliations

Soon will be listed here.

Abstract

The development of paroxysmal nocturnal haemoglobinuria (PNH) requires two coincident factors: somatic mutation of the PIG-A gene in one or more haemopoietic stem cells and an abnormal, hypoplastic bone marrow environment. When both of these conditions are met, the fledgling PNH clone may flourish. This review will discuss the pathophysiology of this disease, which has recently been elucidated in some detail.

Citing Articles

Population pharmacokinetic analyses of pozelimab in patients with CD55-deficient protein-losing enteropathy (CHAPLE disease).

Lin K, Mendell J, Davis J, Harnisch L J Pharmacokinet Pharmacodyn. 2024; 51(6):905-917.

PMID: 39349796 PMC: 11579122. DOI: 10.1007/s10928-024-09941-8.

CD59 gene: 143 haplotypes of 22,718 nucleotides length by computational phasing in 113 individuals from different ethnicities.

Srivastava K, Yin Q, Makuria A, Rios M, Gebremedhin A, Flegel W Transfusion. 2024; 64(7):1296-1305.

PMID: 38817044 PMC: 11251854. DOI: 10.1111/trf.17869.

Acute renal failure in a patient with severe hemolysis.

Kirkizlar O, Kendir M, Karaali Z, Ure U, Ozbay G, Selcuk D Int Urol Nephrol. 2007; 39(2):651-4.

PMID: 17235485 DOI: 10.1007/s11255-006-9096-3.

PIG-A mutations in normal hematopoiesis.

Hu R, Mukhina G, Piantadosi S, Barber J, Jones R, Brodsky R Blood. 2005; 105(10):3848-54.

PMID: 15687243 PMC: 1895084. DOI: 10.1182/blood-2004-04-1472.

Paroxysmal nocturnal hemoglobinuria in a girl with hemolysis and "hematuria".

Dolezel Z, Dostalkova D, Blatny J, Starha J, Gerykova H Pediatr Nephrol. 2004; 19(10):1177-9.

PMID: 15278422 DOI: 10.1007/s00467-004-1563-4.

References

Tremml G, Dominguez C, Rosti V, Zhang Z, Pandolfi P, Keller P . Increased sensitivity to complement and a decreased red blood cell life span in mice mosaic for a nonfunctional Piga gene. Blood. 1999; 94(9):2945-54. View

Englund P . The structure and biosynthesis of glycosyl phosphatidylinositol protein anchors. Annu Rev Biochem. 1993; 62:121-38. DOI: 10.1146/annurev.bi.62.070193.001005. View

Wiedmer T, Hall S, Ortel T, Kane W, Rosse W, Sims P . Complement-induced vesiculation and exposure of membrane prothrombinase sites in platelets of paroxysmal nocturnal hemoglobinuria. Blood. 1993; 82(4):1192-6. View

Johnson R, Rawstron A, Richards S, Morgan G, Norfolk D, Hillmen S . Circulating primitive stem cells in paroxysmal nocturnal hemoglobinuria (PNH) are predominantly normal in phenotype but granulocyte colony-stimulating factor treatment mobilizes mainly PNH stem cells. Blood. 1998; 91(12):4504-8. View

Rosse W . Variations in the red cells in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1973; 24(3):327-42. DOI: 10.1111/j.1365-2141.1973.tb01657.x. View

Socie G, Mary J, de Gramont A, Rio B, Leporrier M, Rose C . Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996; 348(9027):573-7. DOI: 10.1016/s0140-6736(95)12360-1. View

Kawagoe K, Kitamura D, Okabe M, Taniuchi I, Ikawa M, Watanabe T . Glycosylphosphatidylinositol-anchor-deficient mice: implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria. Blood. 1996; 87(9):3600-6. View

Hillmen P, Lewis S, Bessler M, Luzzatto L, Dacie J . Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995; 333(19):1253-8. DOI: 10.1056/NEJM199511093331904. View

Low M . Glycosyl-phosphatidylinositol: a versatile anchor for cell surface proteins. FASEB J. 1989; 3(5):1600-8. DOI: 10.1096/fasebj.3.5.2522071. View

10.

Young N . The problem of clonality in aplastic anemia: Dr Dameshek's riddle, restated. Blood. 1992; 79(6):1385-92. View

11.

Rotoli B, Robledo R, Luzzatto L . Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuria. Blood. 1982; 60(1):157-9. View

12.

HAM T, DINGLE J . STUDIES ON DESTRUCTION OF RED BLOOD CELLS. II. CHRONIC HEMOLYTIC ANEMIA WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: CERTAIN IMMUNOLOGICAL ASPECTS OF THE HEMOLYTIC MECHANISM WITH SPECIAL REFERENCE TO SERUM COMPLEMENT. J Clin Invest. 1939; 18(6):657-72. PMC: 434913. DOI: 10.1172/JCI101081. View

13.

Araten D, Nafa K, Pakdeesuwan K, Luzzatto L . Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci U S A. 1999; 96(9):5209-14. PMC: 21843. DOI: 10.1073/pnas.96.9.5209. View

14.

Dustin M, Selvaraj P, Mattaliano R, Springer T . Anchoring mechanisms for LFA-3 cell adhesion glycoprotein at membrane surface. Nature. 1987; 329(6142):846-8. DOI: 10.1038/329846a0. View

15.

Purow D, Howard T, Marcus S, Rosse W, Ware R . Genetic instability and the etiology of somatic PIG-A mutations in paroxysmal nocturnal hemoglobinuria. Blood Cells Mol Dis. 1999; 25(2):81-91. DOI: 10.1006/bcmd.1999.0229. View

16.

Yamada N, Miyata T, Maeda K, Kitani T, Takeda J, Kinoshita T . Somatic mutations of the PIG-A gene found in Japanese patients with paroxysmal nocturnal hemoglobinuria. Blood. 1995; 85(4):885-92. View

17.

Iida Y, Takeda J, Miyata T, Inoue N, Nishimura J, Kitani T . Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria. Blood. 1994; 83(11):3126-31. View

18.

Dacie J . Paroxysmal nocturnal haemoglobinuria. Proc R Soc Med. 1963; 56:587-96. PMC: 1897256. View

19.

Yamashina M, Ueda E, Kinoshita T, Takami T, Ojima A, Ono H . Inherited complete deficiency of 20-kilodalton homologous restriction factor (CD59) as a cause of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1990; 323(17):1184-9. DOI: 10.1056/NEJM199010253231707. View

20.

Nishimura J, Murakami Y, Kinoshita T . Paroxysmal nocturnal hemoglobinuria: An acquired genetic disease. Am J Hematol. 1999; 62(3):175-82. DOI: 10.1002/(sici)1096-8652(199911)62:3<175::aid-ajh7>3.0.co;2-8. View