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Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia

Background: The pTα/preTCR regulates the β-selection, a crucial T-cell developmental checkpoint, providing a most potent survival advantage to thymocytes mediated by the src-kinase p56(Lck). Methods: To define the relevance of pTα in human T-cell lymphoblastic leukemia (T-ALL), we analyzed in T-ALL...

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Autores principales: Ivanyi, Philipp, Morgan, Michael, Piao, Wenji, Ukena, Sya N., Steube, Klaus, Ganser, Arnold, Franzke, Anke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619105/
https://www.ncbi.nlm.nih.gov/pubmed/20208138
http://dx.doi.org/10.3233/CLO-2009-0500
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author Ivanyi, Philipp
Morgan, Michael
Piao, Wenji
Ukena, Sya N.
Steube, Klaus
Ganser, Arnold
Franzke, Anke
author_facet Ivanyi, Philipp
Morgan, Michael
Piao, Wenji
Ukena, Sya N.
Steube, Klaus
Ganser, Arnold
Franzke, Anke
author_sort Ivanyi, Philipp
collection PubMed
description Background: The pTα/preTCR regulates the β-selection, a crucial T-cell developmental checkpoint, providing a most potent survival advantage to thymocytes mediated by the src-kinase p56(Lck). Methods: To define the relevance of pTα in human T-cell lymphoblastic leukemia (T-ALL), we analyzed in T-ALL cell lines (n=14) pTα and p56(Lck) mRNA and protein expression as also the tyrosine-phosphorylation. The p56(Lck) specific src-protein-tyrosine kinase inhibitor (PTK-I) PP1 was used in growth inhibition assays. IC50 value determination, cell cycle- and apoptosis analyses were performed in T-ALL-, non-T-ALL- and murine transgenic cell lines. Results: pTα expression patterns were markedly different in T-ALL cell lines as compared to those reported for normal lymphoid counterparts. PP1 induced in 6/11 T-ALL cell lines a survival disadvantage resulting from a cell cycle arrest in the G1/0 phase in thymic lymphoblastic cells and apoptosis induction in the immature cell line HSB-2, respectively. PP1 sensitive cell lines expressed the target protein p56(Lck) and showed a corresponding P-Tyr signal. Conclusions: Sensitivity of thymic T-ALLs to PP1 clearly underlines the impact of pTα mediated proliferation in this leukemic sub-type. In addition, p56(Lck) represents also independently of pTα a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases.
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spelling pubmed-46191052016-01-12 Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia Ivanyi, Philipp Morgan, Michael Piao, Wenji Ukena, Sya N. Steube, Klaus Ganser, Arnold Franzke, Anke Cell Oncol Other Background: The pTα/preTCR regulates the β-selection, a crucial T-cell developmental checkpoint, providing a most potent survival advantage to thymocytes mediated by the src-kinase p56(Lck). Methods: To define the relevance of pTα in human T-cell lymphoblastic leukemia (T-ALL), we analyzed in T-ALL cell lines (n=14) pTα and p56(Lck) mRNA and protein expression as also the tyrosine-phosphorylation. The p56(Lck) specific src-protein-tyrosine kinase inhibitor (PTK-I) PP1 was used in growth inhibition assays. IC50 value determination, cell cycle- and apoptosis analyses were performed in T-ALL-, non-T-ALL- and murine transgenic cell lines. Results: pTα expression patterns were markedly different in T-ALL cell lines as compared to those reported for normal lymphoid counterparts. PP1 induced in 6/11 T-ALL cell lines a survival disadvantage resulting from a cell cycle arrest in the G1/0 phase in thymic lymphoblastic cells and apoptosis induction in the immature cell line HSB-2, respectively. PP1 sensitive cell lines expressed the target protein p56(Lck) and showed a corresponding P-Tyr signal. Conclusions: Sensitivity of thymic T-ALLs to PP1 clearly underlines the impact of pTα mediated proliferation in this leukemic sub-type. In addition, p56(Lck) represents also independently of pTα a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases. IOS Press 2010 2010-02-04 /pmc/articles/PMC4619105/ /pubmed/20208138 http://dx.doi.org/10.3233/CLO-2009-0500 Text en Copyright © 2010 Hindawi Publishing Corporation and the authors.
spellingShingle Other
Ivanyi, Philipp
Morgan, Michael
Piao, Wenji
Ukena, Sya N.
Steube, Klaus
Ganser, Arnold
Franzke, Anke
Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
title Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
title_full Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
title_fullStr Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
title_full_unstemmed Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
title_short Pre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
title_sort pre t-cell receptor alpha (ptα) expression patterns and functional analysis in human t-cell lymphoblastic leukemia
topic Other
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619105/
https://www.ncbi.nlm.nih.gov/pubmed/20208138
http://dx.doi.org/10.3233/CLO-2009-0500
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