title: Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase.
abstract: The intracellular signals governing cellular proliferation and developmental progression during lymphocyte development are incompletely understood. The tyrosine kinase Blk is expressed preferentially in the B lineage, but its function in B cell development has been largely unexplored. We have generated transgenic mice expressing constitutively active Blk [Blk(Y495F)] in the B and T lymphoid compartments. Expression of Blk(Y495F) in the B lineage at levels similar to that of endogenous Blk induced B lymphoid tumors of limited clonality, whose phenotypes are characteristic of B cell progenitors at the proB/preB-I to preB-II transition. Expression of constitutively active Blk in the T lineage resulted in the appearance of clonal, thymic lymphomas composed of intermediate single positive cells. Taken together, these results indicate that specific B and T cell progenitor subsets are preferentially susceptible to transformation by Blk(Y495F) and suggest a role for Blk in the control of proliferation during B cell development.
authors.affiliation: Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Malek
authors.forename: D I
authors.initials: DI
authors.lastname: Dordai
authors.forename: J
authors.initials: J
authors.lastname: Reim
authors.forename: H
authors.initials: H
authors.lastname: Dintzis
authors.forename: S
authors.initials: S
authors.lastname: Desiderio
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004789:Enzyme Activation; D015870:Gene Expression; D015321:Gene Rearrangement; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000166:cytology; D019076:Transgenes; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014443:Tyrosine; C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases