Expression of human recombination activating genes (RAG1 and RAG2) in
neoplastic lymphoid cells: correlation with cell differentiation and
antigen receptor expression
JC Bories, JM Cayuela, P Loiseau and F Sigaux
Molecular Hematology Laboratory, Hopital Saint Louis, Paris, France.
Regulation of V-(D)-J recombinations that occur in antigen receptor
encoding genes remains poorly understood. Recently, two genes, RAG1 and
RAG2, that are able to activate rearrangement of synthetic recombination
substrates were cloned in mouse and a human gene homologous to RAG1 was
described. To define the differentiation stages corresponding to RAG1 and
RAG2 RNA expression, we have studied a large number of B- and T-lymphoid
neoplasias. First, we show that a human gene homologous to the murine RAG2
is transcribed in humans. Moreover, using a polymerase chain reaction
approach, we have shown that RAG are expressed not only in T-cell receptor
(TCR)-negative T-cell acute lymphoblastic leukemias (T-ALLs), but also in
some cases in which a significant percentage of cells expressed surface
TCR. Absence of RAG expression was shown in certain T-ALLs at variable
stages of thymic differentiation. Data obtained in B-lineage ALLs show that
RAG RNAs are expressed in almost all slg- B-lineage ALLs but are not
transcribed in the slg+ B-cell proliferations tested, including Burkitt's
ALLs, follicular center cell lymphomas, and chronic leukemias. These
findings are consistent with the involvement of RAG in the control of in
vivo V- (D)-J recombinations. These findings are also of interest in the
delineation of potential regulatory factors acting on RAG transcription and
in the understanding of the mechanisms of specific chromosomal
abnormalities occurring in immature lymphoid cells.
Volume 78,
Issue 8,
pp. 2053-2061,
10/15/1991
Copyright © 1991 by The American Society of Hematology
