Rearrangement of T cell receptor beta, gamma, and delta gene loci in human pre-T cell acute lymphoblastic leukemia.
Configuration of the T cell receptor (TCR) beta, gamma, and delta chain genes, as well as immunoglobulin (Ig) heavy and light chain genes, was studied in 29 cases of E rosette-negative (pre-T cell) acute lymphoblastic leukemias that lack early B cell (CD19), myeloid (CD33), as well as most T cell associated membrane antigens such as CD1, C4, and CD8, but express CD7, cytoplasmic CD3 (cCD3), and TdT strongly, as well as CD5 and/or CD2 heterogeneously. Hematopoietic progenitor cell markers, namely HLA-DR, J5 (CD10), and My10 (CD34), further characterized this immature T ALL of putative prothymocytic phenotype. Eleven ALLs showed a germline configuration of TCR as well as Ig genes. In three cases, only TCR delta sequences were rearranged, and four additional cases were characterized by recombination of both, TCR gamma as well as TCR delta sequences. Eleven patients showed concurrent rearrangements of TCR beta, gamma, and delta chain genes. An Ig heavy chain rearrangement was observed in one case. These data support the hypothesis that, analogous to pre-B development, a cascade of TCR rearrangements occurs in pre-T cells. Moreover, findings reported here suggest that CD7, as well as CD2 and CD5, antigens appear on precursor cells prior to entry into the thymus and support a model for the developmental hierarchy of TCR genes during early T cell ontogeny.
Raghavachar
A
A
Department of Transfusion Medicine, University of Ulm, FRG.
Thiel
E
E
Hansen-Hagge
T E
TE
Kranz
B
B
Bartram
C R
CR
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015139:Blotting, Southern; D002874:Chromosome Mapping; D015342:DNA Probes; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D015329:Gene Rearrangement, T-Lymphocyte; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000276:immunology; D011289:Preleukemia / Q000235:genetics* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D015342:DNA Probes; D011948:Receptors, Antigen, T-Cell