Identification of novel regulators in T-cell differentiation of aplastic anemia patients

<p>Abstract</p> <p>Background</p> <p>Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular imm...

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Main Authors: Probst-Kepper Michael, Grosse Jens, Ivanyi Philipp, Piao Wenji, Pförtner Susanne, Hunger J Katrin, Geffers Robert, Franzke Anke, Ganser Arnold, Buer Jan
Format: Article
Language:English
Published: BMC 2006-10-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/7/263
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author Probst-Kepper Michael
Grosse Jens
Ivanyi Philipp
Piao Wenji
Pförtner Susanne
Hunger J Katrin
Geffers Robert
Franzke Anke
Ganser Arnold
Buer Jan
author_facet Probst-Kepper Michael
Grosse Jens
Ivanyi Philipp
Piao Wenji
Pförtner Susanne
Hunger J Katrin
Geffers Robert
Franzke Anke
Ganser Arnold
Buer Jan
author_sort Probst-Kepper Michael
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular immune response. To overcome this technical problem we performed a microarray analysis of CD3<sup>+ </sup>T-cells derived from bone marrow aspirates and peripheral blood samples of newly diagnosed AA patients and healthy volunteers. Two AA patients were additionally analyzed after achieving a partial remission following immunosuppression. The regulation of selected candidate genes was confirmed by real-time RT-PCR.</p> <p>Results</p> <p>Among more than 22.200 transcripts, 583 genes were differentially expressed in the bone marrow of AA patients compared to healthy controls. Dysregulated genes are involved in T-cell mediated cytotoxicity, immune response of Th1 differentiated T-cells, and major regulators of immune function. In hematological remission the expression levels of several candidate genes tend to normalize, such as immune regulators and genes involved in proinflammatory immune response.</p> <p>Conclusion</p> <p>Our study suggests a pivotal role of Th1/Tc1 differentiated T-cells in immune-mediated marrow destruction of AA patients. Most importantly, immune regulatory genes could be identified, which are likely involved in the recovery of hematopoiesis and may help to design new therapeutic strategies in bone marrow failure syndromes.</p>
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spelling doaj.art-46d5f0500cf5486db6faa8cc0acf79702022-12-22T03:26:20ZengBMCBMC Genomics1471-21642006-10-017126310.1186/1471-2164-7-263Identification of novel regulators in T-cell differentiation of aplastic anemia patientsProbst-Kepper MichaelGrosse JensIvanyi PhilippPiao WenjiPförtner SusanneHunger J KatrinGeffers RobertFranzke AnkeGanser ArnoldBuer Jan<p>Abstract</p> <p>Background</p> <p>Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular immune response. To overcome this technical problem we performed a microarray analysis of CD3<sup>+ </sup>T-cells derived from bone marrow aspirates and peripheral blood samples of newly diagnosed AA patients and healthy volunteers. Two AA patients were additionally analyzed after achieving a partial remission following immunosuppression. The regulation of selected candidate genes was confirmed by real-time RT-PCR.</p> <p>Results</p> <p>Among more than 22.200 transcripts, 583 genes were differentially expressed in the bone marrow of AA patients compared to healthy controls. Dysregulated genes are involved in T-cell mediated cytotoxicity, immune response of Th1 differentiated T-cells, and major regulators of immune function. In hematological remission the expression levels of several candidate genes tend to normalize, such as immune regulators and genes involved in proinflammatory immune response.</p> <p>Conclusion</p> <p>Our study suggests a pivotal role of Th1/Tc1 differentiated T-cells in immune-mediated marrow destruction of AA patients. Most importantly, immune regulatory genes could be identified, which are likely involved in the recovery of hematopoiesis and may help to design new therapeutic strategies in bone marrow failure syndromes.</p>http://www.biomedcentral.com/1471-2164/7/263
spellingShingle Probst-Kepper Michael
Grosse Jens
Ivanyi Philipp
Piao Wenji
Pförtner Susanne
Hunger J Katrin
Geffers Robert
Franzke Anke
Ganser Arnold
Buer Jan
Identification of novel regulators in T-cell differentiation of aplastic anemia patients
BMC Genomics
title Identification of novel regulators in T-cell differentiation of aplastic anemia patients
title_full Identification of novel regulators in T-cell differentiation of aplastic anemia patients
title_fullStr Identification of novel regulators in T-cell differentiation of aplastic anemia patients
title_full_unstemmed Identification of novel regulators in T-cell differentiation of aplastic anemia patients
title_short Identification of novel regulators in T-cell differentiation of aplastic anemia patients
title_sort identification of novel regulators in t cell differentiation of aplastic anemia patients
url http://www.biomedcentral.com/1471-2164/7/263
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