title: Pre T-cell receptor alpha (pTalpha) expression patterns and functional analysis in human T-cell lymphoblastic leukemia.
abstract: BACKGROUND
  The pTalpha/preTCR regulates the beta-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 pTalpha in human T-cell lymphoblastic leukemia (T-ALL), we analyzed in T-ALL cell lines (n=14) pTalpha 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. IC(50) value determination, cell cycle- and apoptosis analyses were performed in T-ALL-, non-T-ALL- and murine transgenic cell lines.
  
  
  RESULTS
  pTalpha 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 G(1/0) 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 pTalpha mediated proliferation in this leukemic sub-type. In addition, p56(Lck) represents also independently of pTalpha a promising therapeutical target for the src-kinase inhibitors in neoplastic lymphoid diseases.
authors.affiliation: Clinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ivanyi
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.forename: Wenji
authors.initials: W
authors.lastname: Piao
authors.forename: Sya N
authors.initials: SN
authors.lastname: Ukena
authors.forename: Klaus
authors.initials: K
authors.lastname: Steube
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism*; D013601:T-Lymphocytes
chemical_list: D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)