Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97487
Title:
Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.
Authors:
Raghavachar, A; Janssen, J W; Schrezenmeier, H; Wagner, B; Bartram, C R; Schulz, A S; Hein, C; Cowling, Graham J; Mubarik, A; Testa, Nydia G; Dexter, T Michael; Hows, J M; Marsh, Judith C W
Abstract:
We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.
Affiliation:
Department of Medicine III, University of Ulm, Germany.
Citation:
Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia. 1995, 86 (8):2938-47 Blood
Journal:
Blood
Issue Date:
15-Oct-1995
URI:
http://hdl.handle.net/10541/97487
PubMed ID:
7579386
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRaghavachar, Aen
dc.contributor.authorJanssen, J Wen
dc.contributor.authorSchrezenmeier, Hen
dc.contributor.authorWagner, Ben
dc.contributor.authorBartram, C Ren
dc.contributor.authorSchulz, A Sen
dc.contributor.authorHein, Cen
dc.contributor.authorCowling, Graham Jen
dc.contributor.authorMubarik, Aen
dc.contributor.authorTesta, Nydia Gen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorHows, J Men
dc.contributor.authorMarsh, Judith C Wen
dc.date.accessioned2010-04-27T14:08:39Z-
dc.date.available2010-04-27T14:08:39Z-
dc.date.issued1995-10-15-
dc.identifier.citationClonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia. 1995, 86 (8):2938-47 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid7579386-
dc.identifier.urihttp://hdl.handle.net/10541/97487-
dc.description.abstractWe evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.en
dc.language.isoenen
dc.subjectAplastic Anaemiaen
dc.subjectHaematopoiesisen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAnemia, Aplastic-
dc.subject.meshBase Sequence-
dc.subject.meshClone Cells-
dc.subject.meshDosage Compensation, Genetic-
dc.subject.meshFemale-
dc.subject.meshGenetic Markers-
dc.subject.meshHematopoiesis-
dc.subject.meshHumans-
dc.subject.meshMethylation-
dc.subject.meshMiddle Aged-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshPhosphoglycerate Kinase-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshX Chromosome-
dc.titleClonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medicine III, University of Ulm, Germany.en
dc.identifier.journalBlooden

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