Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure.
Chiharu Sugimori,Kanako Mochizuki,Zhirong Qi,Naomi Sugimori,Ken Ishiyama,Yukio Kondo,Hirohito Yamazaki,Akiyoshi Takami,Hirokazu Okumura,Shinji Nakao +9 more
TLDR
The findings suggest that the PNH‐type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self‐maintenance properties of the individual PIG a mutants.Abstract:
Peripheral blood from 489 recently diagnosed patients with aplastic anaemia (AA) and 316 with refractory anaemia (RA) of myelodysplastic syndrome was evaluated to characterize CD55(-)CD59(-) [paroxysmal nocturnal haemoglobinuria (PNH)]-type blood cells associated with bone marrow (BM) failure. PNH-type cells were detected in 57% and 20% of patients with AA and RA, respectively. The percentages of PNH-type granulocytes ranged from 0.003% to 94.2% and the distribution was log-normal with a median of 0.178%. Serial analyses of 75 patients with PNH-type cells over 5 years revealed that the percentage of PNH-type cells constantly increased in 13 (17%), persisted in 44 (59%), disappeared in the remaining 18 (24%) although even in the 'Disappearance' group, PNH-type granulocytes persisted for at least 6 months. A scattergram profile of PNH-type cells unique to each patient persisted regardless of the response to immunosuppressive therapy and only single PIGA mutations were detected in PNH-type granulocytes sorted from four patients. These findings suggest that the PNH-type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self-maintenance properties of the individual PIGA mutants.read more
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Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry.
Michael J. Borowitz,Fiona E. Craig,Joseph A. DiGiuseppe,Andrea Illingworth,Wendell F. Rosse,D. Robert Sutherland,Carl T. Wittwer,Stephen J. Richards +7 more
TL;DR: Flow cytometry is the method of choice for identifying cells deficient in GPI‐linked proteins and is, therefore, necessary for the diagnosis of PNH, but to date there has not been an attempt to standardize the methodology used to identify these cells.
Journal ArticleDOI
Clonal hematopoiesis in acquired aplastic anemia
TL;DR: High frequency of 6pUPD and overrepresentation of PIGA and BCOR/BCORL1 mutations are unique to AA, suggesting the role of autoimmunity in clonal selection and DNMT3A and ASXL1 mutations indicate a close link to CH in the aged bone marrow, in terms of the mechanism for selection.
Journal ArticleDOI
Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria
TL;DR: An understanding of the unique pathobiology of PNH in relationship both to complement physiology and immune-mediated bone marrow failure provides the basis for a systematic approach to management.
Journal ArticleDOI
Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study.
A. D. Kulagin,Igor Lisukov,Maria Ivanova,Irina K. Golubovskaya,Irina Kruchkova,Sergey N. Bondarenko,V N Vavilov,N V Stancheva,Elena V. Babenko,Alexandra A. Sipol,Natalia Pronkina,Vladimir A. Kozlov,Boris V. Afanasyev +12 more
TL;DR: A prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST) confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.
Journal ArticleDOI
Natural history of paroxysmal nocturnal hemoglobinuria clones in patients presenting as aplastic anemia
TL;DR: The risk of developing clinically significant PNH after HiCy therapy appears to be low in AA patients with PNH clones, especially for those with small initial PNH clone sizes and for those who respond to hiCy therapy.
References
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John M. Bennett,Daniel Catovsky,Marie-Theregse Daniel,G. Flandrin,David A. G. Galton,Harvey R. Gralnick,C. Sultan +6 more
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Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.
Junji Takeda,Toshio Miyata,Kazuyoshi Kawagoe,Yoshiyasu Iida,Yoshiyasu Iida,Yuichi Endo,Teizo Fujita,Minoru Takahashi,Teruo Kitani,Taroh Kinoshita +9 more
TL;DR: It is reported that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria.
Journal ArticleDOI
Natural history of paroxysmal nocturnal hemoglobinuria.
TL;DR: PNH is a chronic disorder that curtails life, and a spontaneous long-term remission can occur, which must be taken into account when considering potentially dangerous treatments, such as bone marrow transplantation.
Journal ArticleDOI
Diagnosis and management of paroxysmal nocturnal hemoglobinuria.
Charles J. Parker,Mitsuhiro Omine,Stephen J. Richards,Junichi Nishimura,Monica Bessler,Russell E. Ware,Peter Hillmen,Lucio Luzzatto,Neal S. Young,Taroh Kinoshita,Wendell F. Rosse,Gérard Socié +11 more
TL;DR: The primary clinical manifestations of paroxysmal nocturnal hemoglobinuria are hemolytic anemia, marrow failure, and thrombophilia.
Journal ArticleDOI
Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals.
TL;DR: Using flow cytometric analysis of granulocytes, it is identified cells that have the PNH phenotype, and PNH red blood cells also were identified, showing clearly that PIG-A gene mutations are not sufficient for the development of PNH.