Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita

Frederick D Goldman; Geraldine Aubert; Al J Klingelhutz; Mark Hills; Sarah R Cooper; Wendy S Hamilton; Annette J Schlueter; Karen Lambie; Connie J Eaves; Peter M Lansdorp

doi:10.1182/blood-2007-10-120204

Back

Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita

Journal article

Open access

Peer reviewed

Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita

Frederick D Goldman, Geraldine Aubert, Al J Klingelhutz, Mark Hills, Sarah R Cooper, Wendy S Hamilton, Annette J Schlueter, Karen Lambie, Connie J Eaves and Peter M Lansdorp

Blood, Vol.111(9), pp.4523-4531

05/01/2008

DOI: 10.1182/blood-2007-10-120204

PMCID: PMC2343591

PMID: 18310499

Files and links (1)

url

https://doi.org/10.1182/blood-2007-10-120204View

Published (Version of record) Open Access

Abstract

Dyskeratosis congenita (DC) is an inherited bone marrow (BM) failure syndrome associated with mutations in telomerase genes and the acquisition of shortened telomeres in blood cells. To investigate the basis of the compromised hematopoiesis seen in DC, we analyzed cells from granulocyte colony-stimulating factor mobilized peripheral blood (mPB) collections from 5 members of a family with autosomal dominant DC with a hTERC mutation. Premobilization BM samples were hypocellular, and percentages of CD34(+) cells in marrow and mPB collections were significantly below values for age-matched controls in 4 DC subjects. Directly clonogenic cells, although present at normal frequencies within the CD34(+) subset, were therefore absolutely decreased. In contrast, even the frequency of long-term culture-initiating cells within the CD34(+) DC mPB cells was decreased, and the telomere lengths of these cells were also markedly reduced. Nevertheless, the different lineages of mature cells were produced in normal numbers in vitro. These results suggest that marrow failure in DC is caused by a reduction in the ability of hematopoietic stem cells to sustain their numbers due to telomere impairment rather than a qualitative defect in their commitment to specific lineages or in the ability of their lineage-restricted progeny to execute normal differentiation programs.

Antigens, CD34 - analysis

Telomerase - genetics

Hematopoiesis

Humans

Granulocyte Colony-Stimulating Factor

Dyskeratosis Congenita - pathology

Hematopoietic Stem Cells - pathology

Hematopoietic Stem Cell Mobilization

Mutation

RNA - genetics

Details

Title: Subtitle: Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita
Creators: Frederick D Goldman - Department of Pediatrics, Division of Hematology/Oncology, University of Iowa Children's Hospital, Iowa City 52242, USA. frederick-goldman@uiowa.edu
Geraldine Aubert
Al J Klingelhutz
Mark Hills
Sarah R Cooper
Wendy S Hamilton
Annette J Schlueter
Karen Lambie
Connie J Eaves
Peter M Lansdorp
Resource Type: Journal article
Publication Details: Blood, Vol.111(9), pp.4523-4531
Publisher: United States
DOI: 10.1182/blood-2007-10-120204
PMID: 18310499
PMCID: PMC2343591
ISSN: 0006-4971
eISSN: 1528-0020
Grant note: R21 AI029524 / NIAID NIH HHS AI29524 / NIAID NIH HHS R01 AI029524 / NIAID NIH HHS
Language: English
Date published: 05/01/2008
Academic Unit: Microbiology and Immunology; Pathology; Radiation Oncology; Obstetrics and Gynecology
Record Identifier: 9984001143002771

Metrics

26 Record Views

44 Times Cited - Web of Science