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CD3+ leukemic large granular lymphocytes utilize diverse T-cell receptor V
beta genes
MP Davey, G Starkebaum and TP Loughran
Department of Medicine, Oregon Health Sciences University, Portland.
CD3+ large granular lymphocyte (LGL) leukemia is a disease of unknown
etiology characterized by clonal proliferation of T cells that usually
express T-cell receptor (TCR) alpha beta heterodimers. The purpose of this
study was to identify the variable (V), joining (J), and diversity (D)
region TCR beta-chain genes expressed by CD3+ LGL leukemic cells in an
attempt to gain insights into the etiology of this disorder. Twelve
patients with LGL leukemia were studied, including seven with both LGL
leukemia and rheumatoid arthritis (RA). RA is also a disease of unknown
etiology that occurs frequently in patients with LGL leukemia. Clonally
expanded T cells that express specific TCR V beta genes have been
identified in fluid and tissue specimens from the joints of patients with
RA. In this study, V beta expression was determined by PCR using a panel of
22 unique V beta primers to amplify cDNA prepared from peripheral blood
mononuclear cells (PBMC). A dominant V beta gene product was readily
apparent in all patients. To confirm that the dominant V beta gene
originated from a clonal expansion, DNA fragments corresponding to the
dominant V beta genes were subcloned into plasmids and independently
isolated recombinants were sequenced. V-D-J region sequences that occurred
repeatedly indicated clonality. The V beta and J beta genes expressed by
the leukemic cells showed a pattern of distribution that followed the
frequency with which these genes are represented in the peripheral blood.
The residues corresponding to the third complementarity-determining region
of the TCR beta chain were different in all cases. A specific pattern of
VDJ usage was not identified for those patients with both LGL leukemia and
RA; however, utilization of V beta-6 by LGL clones (N = 3) was observed
only in the setting of RA. These data suggest that leukemic CD3+ LGL cells
have been clonally transformed in a random fashion with respect to the TCR
beta chain.
Volume 85,
Issue 1,
pp. 146-150,
01/01/1995
Copyright © 1995 by The American Society of Hematology

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