title: Blockade of thymic stromal lymphopoietin (TSLP) receptor inhibits TSLP-driven proliferation and signalling in lymphoblasts from a subset of B-precursor ALL patients.
abstract: OBJECTIVE
  The cytokine thymic stromal lymphopoietin (TSLP) and its receptor TSLPR are involved in intercellular communication in the course of allergic inflammation and have recently been implicated in the development of various malignancies including B cell precursor acute lymphoblastic leukemia (BCP-ALL). We studied TSLPR expression, TSLP-induced signal transduction and its antibody-mediated inhibition in long-term cultures of primary cells derived from B-precursor ALL patients.
  
  
  METHODS
  TSLPR expression was determined by flow cytometry and Western blot analysis, cell proliferation, signal transduction via the JAK/STAT pathway was analysed by Western blot detection of STAT tyrosine phosphorylation and by measuring TSLP-dependent activation of a STAT-specific reporter gene construct. For inhibition studies a recently introduced antagonistic antibody to the TSLPRα-subunit was used.
  
  
  RESULTS
  TSLPR surface expression was observed in leukemic lymphoblasts from two out of ten patients with BCP-ALL. Upon TSLP stimulation, the cells with the highest TSLPR expression level showed enhanced proliferation and JAK/STAT-mediated gene regulation in a dose-dependent manner. By employment of an inhibitory antibody to the TSLPR, both TSLP-triggered cell proliferation and STAT transcription factor activation were specifically inhibited.
  
  
  CONCLUSIONS
  These results suggest that blockade of the TSLPR might be a therapeutic option for a subset of BCP-ALL patients.
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Vetter
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Borowski
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wohlmann
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Nilabh
authors.initials: N
authors.lastname: Ranjan
authors.affiliation: University of Rostock, Department of Pneumology, Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kuepper
authors.affiliation: Goethe University Frankfurt, Department of Medicine, Hematology and Oncology, Frankfurt, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Badura
authors.affiliation: Goethe University Frankfurt, Department of Medicine, Hematology and Oncology, Frankfurt, Germany.
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany. Electronic address: karlheinz.friedrich@med.uni-jena.de.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Friedrich
mesh_terms: D049109:Cell Proliferation / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D015448:Leukemia, B-Cell / Q000378:metabolism / Q000473:pathology*; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C498762:CRLF2 protein, human; D016207:Cytokines; D018121:Receptors, Cytokine; D000094632:Thymic Stromal Lymphopoietin
keywords: B-precursor ALL; Cytokine receptors; Inhibitory antibody; TSLP