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T-cell receptor gene rearrangement in T-cell large granular leukocyte
leukemia: preferential V alpha but diverse J alpha usage in one of five
patients
C Kasten-Sportes, S Zaknoen, RG Steis, WC Chan, EF Winton and TA Waldmann
Metabolism Branch, National Cancer Institute, Bethesda, MD 20892.
T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of
mature T cells that is associated with neutropenia and autoimmune
phenomena. Although the progression of the lymphoproliferation is indolent,
it is often associated with a monoclonal proliferation of T- cell-type
large granular lymphocytes (LGL) that manifest multiple in vitro suppressor
and cytotoxic activities. We considered the possibility that the
granulocytopenia or anemia might represent an autoimmune disorder mediated
by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen
involved in hematopoiesis. Therefore, in an effort to characterize the
usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD,
we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the
T-cell type LGL of five patients. The five patients studied did not use a
common V alpha nor a common J alpha segment. However, an unusual finding
was observed in one of the patients where the occurrence of a single
variable-diversity-junctional (VDJ) rearrangement of the beta chain
confirmed the monoclonal origin of the LGL proliferation. In accord with
this evidence for monoclonality, many of the cells studied used a common V
alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a
marked diversity of the J alpha segments and N-region addition that were
associated with the V alpha 19.1 segment. This pattern of common V alpha
usage associated with different N and J alpha segments suggests an
immune-mediated selection process affecting the TCR alpha chain occurring
after the transformation event that established the clone. We suggest that
the T-cell-type LGL malignant clone might have developed autoreactivity
conferred by the selected TCR alpha chain and that this autoreactivity
might be implicated in this patient's anemia.
Volume 83,
Issue 3,
pp. 767-775,
02/01/1994
Copyright © 1994 by The American Society of Hematology
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