Table of Contents Author Guidelines Submit a Manuscript
Cellular Oncology
Volume 32 (2010), Issue 1-2, Pages 101-108
http://dx.doi.org/10.3233/CLO-2009-0500

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

Philipp Ivanyi,1 Michael Morgan,1 Wenji Piao,1 Sya N. Ukena,1 Klaus Steube,2 Arnold Ganser,1 and Anke Franzke1

1Clinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hannover, Germany
2DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany

Copyright © 2010 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 p56Lck.

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 p56Lck mRNA and protein expression as also the tyrosine-phosphorylation. The p56Lck 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 p56Lck 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, p56Lck represents also independently of pTα a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases.