Engagement of the CD19 Receptor on Human B-Lineage Leukemia Cells Activates LCK Tyrosine Kinase and Facilitates Radiation-Induced Apoptosis

As presently reported, both ionizing radiation and engagement of the CD19 receptor are capable of inducing apoptosis in B-lineage acute lymphoblastic leukemia (ALL) cells. In both instances, activation of tyrosine kinases appears to be a proximal and mandatory step, since it can be prevented by the...

Full description

Saved in:
Bibliographic Details
Published in:Radiation research 1993-12, Vol.136 (3), p.313-319
Main Authors: Waddick, Kevin G., Chae, HeonJoo Park, Tuel-Ahlgren, Lisa, Jarvis, Lisa J., Dibirdik, Ilker, Myers, Dorothea E., Uckun, Fatih M.
Format: Article
Language:English
Subjects:
Antigens, CD - physiology
Antigens, CD19
Antigens, Differentiation, B-Lymphocyte - physiology
Apoptosis
Apoptosis - radiation effects
B lymphocytes
Biological and medical sciences
Blasts
Burkitt Lymphoma - enzymology
Burkitt Lymphoma - pathology
Cell lines
DNA
Enzyme Activation
Ionizing radiation
Leukemia
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Lymphocytic leukemia
Medical sciences
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins - metabolism
Radiation therapy and radiosensitizing agent
Radiation Tolerance
Receptors
Space life sciences
Symposium: Apoptosis/Programmed Cell Death
Treatment with physical agents
Treatment. General aspects
Tumor Cells, Cultured
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:As presently reported, both ionizing radiation and engagement of the CD19 receptor are capable of inducing apoptosis in B-lineage acute lymphoblastic leukemia (ALL) cells. In both instances, activation of tyrosine kinases appears to be a proximal and mandatory step, since it can be prevented by the tyrosine kinase inhibitor genistein. This common biochemical signaling pathway involves the rapid activation of the Src family tyrosine kinase LCK ( p56 lck), which is physically associated with the CD19 receptor, and enhanced tyrosine phosphorylation of multiple substrates leading to stimulation of phosphoinositide turnover, and activation of protein kinase C. Importantly, engagement of the CD19 receptor promoted radiation-induced apoptosis in radiation-resistant B-lineage ALL cells in a cell type-specific fashion. Our results prompt the hypothesis that clonogenic B-lineage ALL blasts with an inherent or acquired resistance to radiation could be radiosensitized in clinical settings using anti-CD19 MoAb B43 or its homoconjugate as adjuncts.
ISSN:0033-7587
1938-5404
DOI:10.2307/3578542