Paroxysmal Nocturnal Hemoglobinuria: Biology and Treatment

被引：4
作者：
Bravo-Perez, Carlos [1 ,2 ]
Guarnera, Luca [1 ,3 ]
Williams, Nakisha D. [1 ]
Visconte, Valeria [1 ]
机构：
[1] Cleveland Clin, Taussig Canc Inst, Dept Translat Hematol & Oncol Res, Cleveland, OH 44114 USA
[2] Univ Murcia, Dept Hematol & Med Oncol, Hosp Univ Morales Meseguer, IMIB Pascual Parrilla,CIBERER Inst Salud Carlos II, Murcia 30005, Spain
[3] Univ Roma Tor Vergata, Dept Biomed & Prevent, Hematol, I-00133 Rome, Italy
来源：
MEDICINA-LITHUANIA | 2023年 / 59卷 / 09期
关键词：
paroxysmal nocturnal hemoglobinuria; biology; treatment; COMPLEMENT INHIBITOR ECULIZUMAB; NATURAL-KILLER-CELLS; PIG-A MUTATION; APLASTIC-ANEMIA; JAPANESE PATIENTS; GENE MUTATION; BLOOD-CELLS; T-CELLS; APOPTOSIS; RESISTANCE;
D O I：
10.3390/medicina59091612
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal hematopoietic disorder characterized by the lack of glycosylphosphatidylinositol-anchored proteins (GPI-APs) as a consequence of somatic mutations in the phosphatidylinositol glycan anchor biosynthesis class A (PIGA) gene. Clinical manifestations of PNH are intravascular hemolysis, thrombophilia, and bone marrow failure. Treatment of PNH mainly relies on the use of complement-targeted therapy (C5 inhibitors), with the newest agents being explored against other factors involved in the complement cascade to alleviate unresolved intravascular hemolysis and extravascular hemolysis. This review summarizes the biology and current treatment strategies for PNH with the aim of reaching a general audience with an interest in hematologic disorders.
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页数：14
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共 85 条
[1]   The biogenesis of the immunopeptidome [J].
Admon, Arie .
SEMINARS IN IMMUNOLOGY, 2023, 67
[2]   Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals [J].
Araten, DJ ;
Nafa, K ;
Pakdeesuwan, K ;
Luzzatto, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) :5209-5214
[3]   Emergence of clonal hematopoiesis in the majority of patients with acquired aplastic anemia [J].
Babushok, Dana V. ;
Perdigones, Nieves ;
Perin, Juan C. ;
Olson, Timothy S. ;
Ye, Wenda ;
Roth, Jacquelyn J. ;
Lind, Curt ;
Cattier, Carine ;
Li, Yimei ;
Hartung, Helge ;
Paessler, Michele E. ;
Frank, Dale M. ;
Xie, Hongbo M. ;
Cross, Shanna ;
Cockroft, Joshua D. ;
Podsakoff, Gregory M. ;
Monos, Dimitrios ;
Biegel, Jaclyn A. ;
Mason, Philip J. ;
Bessler, Monica .
CANCER GENETICS, 2015, 208 (04) :115-128
[4]   Somatic HLA mutations expose the role of class I-mediated autoimmunity in aplastic anemia and its clonal complications [J].
Babushok, Daria V. ;
Duke, Jamie L. ;
Xie, Hongbo M. ;
Stanley, Natasha ;
Atienza, Jamie ;
Perdigones, Nieves ;
Nicholas, Peter ;
Ferriola, Deborah ;
Li, Yimei ;
Huang, Hugh ;
Ye, Wenda ;
Morrissette, Jennifer J. D. ;
Kearns, Jane ;
Porter, David L. ;
Podsakoff, Gregory M. ;
Eisenlohr, Laurence C. ;
Biegel, Jaclyn A. ;
Chou, Stella T. ;
Monos, Dimitrios S. ;
Bessler, Monica ;
Olson, Timothy S. .
BLOOD ADVANCES, 2017, 1 (22) :1900-1910
[5]   Ankylosing spondylitis [J].
Braun, Juergen ;
Sieper, Joachim .
LANCET, 2007, 369 (9570) :1379-1390
[6]   Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria [J].
Brodsky, RA ;
Vala, MS ;
Barber, JP ;
Medof, ME ;
Jones, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (16) :8756-8760
[7]   Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria [J].
Brodsky, Robert A. ;
Young, Neal S. ;
Antonioli, Elisabetta ;
Risitano, Antonio M. ;
Schrezenmeier, Hubert ;
Schubert, Jorg ;
Gaya, Anna ;
Coyle, Luke ;
De Castro, Carlos ;
Fu, Chieh-Lin ;
Maciejewski, Jaroslaw P. ;
Bessler, Monica ;
Kroon, Henk-Andre ;
Rother, Russell P. ;
Hillmen, Peter .
BLOOD, 2008, 111 (04) :1840-1847
[8]   Vemircopan (ALXN2050) Monotherapy in Paroxysmal Nocturnal Hemoglobinuria: Interim Data from a Phase 2 Open-Label Proof-of-Concept Study [J].
Browett, Peter J. ;
Kulasekararaj, Austin ;
Notaro, Rosario ;
Ogawa, Masayo ;
Risitano, Antonio ;
Yu, Ji ;
Lee, Jong Wook .
BLOOD, 2022, 140
[9]   HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events [J].
Buhler, Stephane ;
Sanchez-Mazas, Alicia .
PLOS ONE, 2011, 6 (02)
[10]   Differential gene expression in hematopoietic progenitors from paroxysmal nocturnal hemoglobinuria patients reveals an apoptosis/immune response in 'normal' phenotype cells [J].
Chen, G ;
Zeng, W ;
Maciejewski, JP ;
Kcyvanfar, K ;
Billings, EM ;
Young, NS .
LEUKEMIA, 2005, 19 (05) :862-868
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