T-cell receptor delta/alpha rearrangements in lymphoid neoplasms.
Rearrangements within the T-cell receptor (TCR)delta/alpha locus were analyzed in a wide variety of lymphoid neoplasms by eight DNA probes specific for TCR J delta, J alpha and C alpha segments. In all 11 T-cell malignancies, rearrangement and/or deletion of TCR delta was detected irrespective of the stage of maturation of the tumor. The organization of TCR delta correlated with the phenotype of the tumor: In "prethymic" T-cell acute lymphocytic leukemia (ALL), TCR delta was the only TCR gene to be rearranged. More mature T cell malignancies expressing CD4 together with CD3 showed deletion of both alleles of TCR delta, suggestive of TCR V alpha-J alpha rearrangement. All 43 B-cell tumors expressing surface immunoglobulin (sIg), including two cases of adult B-cell ALL, had germline configuration of TCR delta/alpha. In contrast, all 17 B-cell precursor ALLs (null, common, and pre-B-cell ALLs) had rearrangement and/or deletion of TCR delta/alpha. A single case of "histiocytic" lymphoma also showed biallelic deletion of TCR delta. Oligoclonal rearrangements of Ig and TCR genes were observed in two cases of B-cell precursor ALL and in one case of T-cell lymphoblastic lymphoma. Patterns of such "aberrant" TCR rearrangement were similar to those observed in T-lineage malignancies. In particular, seven of eight cases of B-cell precursor ALL and the histiocytic lymphoma which demonstrated biallelic TCR delta deletion, (suggestive of a V alpha-J alpha rearrangement) had clonal TCR beta rearrangement. These data support the hypothesis that supposedly aberrant rearrangements of the TCR genes may follow the same developmental controls as found in T-cell differentiation, despite the lack of evidence for further commitment to the T-cell lineage. TCR delta rearrangement is a useful marker of clonality of immature T-cell tumors which may have only this gene rearranged but is not specific to the T-cell lineage.
Dyer
M J
MJ
Department of Haematology, University of Cambridge, England.
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002648:Child; D003593:Cytoplasm / Q000032:analysis; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D006801:Humans; D007938:Leukemia / Q000145:classification / Q000235:genetics*; D015448:Leukemia, B-Cell / Q000145:classification / Q000235:genetics; D015458:Leukemia, T-Cell / Q000145:classification / Q000235:genetics; D008223:Lymphoma / Q000145:classification / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000032:analysis; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D000945:Antigens, Differentiation, T-Lymphocyte; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell