Open AccessPre T-Cell Receptor Alpha (pTα) Expression Patterns and Functional Analysis in Human T-Cell Lymphoblastic Leukemia
Author(s) -
Philipp Ivanyi,
Michael Morgan,
Wenji Piao,
Sya N. Ukena,
Klaus G. Steube,
Arnold Ganser,
Anke Franzke
Publication year - 2010
Publication title -
analytical cellular pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.576
H-Index - 24
eISSN - 2210-7185
pISSN - 2210-7177
DOI - 10.1155/2010/309071
Subject(s) - t cell , cancer research , cell culture , tyrosine kinase , t cell receptor , biology , apoptosis , cell growth , t cell leukemia , cytotoxic t cell , microbiology and biotechnology , signal transduction , leukemia , immunology , in vitro , immune system , biochemistry , genetics
Background : The pT α /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 pT α 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 : pT α 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 pT α mediated proliferation in this leukemic sub-type. In addition, p56 Lck represents also independently of pT α a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases.