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PMID: 9636152 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 13 ·1998-06-23 ·Pages 7351-6

Malek SN, Dordai DI, Reim J, Dintzis H, Desiderio S

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.

MeSH Terms
Animals B-Lymphocytes/cytology Cell Division Cell Transformation, Neoplastic Clone Cells Enzyme Activation Gene Expression Gene Rearrangement Hematopoietic Stem Cells/enzymology Mice Mice, Nude Mice, Transgenic Phosphorylation T-Lymphocytes/cytology Transgenes Tyrosine/metabolism src-Family Kinases/genetics,metabolism
Chemicals
Tyrosine protein-tyrosine kinase p55(blk) src-Family Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Malek S N
Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dordai D I
Reim J
Dintzis H
Desiderio S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.13.7351
Published
1998-06-23
Pages
7351-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22613
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.13.7351 PMC Full Text View journal details
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