Human T cell gamma genes are frequently rearranged in B-lineage acute lymphoblastic leukemias but not in chronic B cell proliferations.
T cell rearranging gene gamma (TRG gamma) and T cell antigen receptor beta (TCR beta) chain gene rearrangement and transcription were studied in a series of patients with B-lineage acute lymphoblastic leukemia (ALL), in which the Ig H chain genes are rearranged and the surface phenotype reproduces the stages of normal pre-B maturation. For comparison, polyclonal T cells from peripheral blood of healthy donors and blast cells from 19 cases of T lineage ALL were also studied. In this study we demonstrate the presence of a clonal rearrangement of the TRG gamma in 18 of the 22 B-lineage ALL cases and establish that this rearrangement, which generally involves the J gamma 1 region, is often monoallelic and appears different from the biallelic J gamma 2 rearrangement frequently seen in T-cell ALLs. In 9 of 22 cases, we found rearrangement of the genes of the TCR beta chain, which never involved the J beta 1 region. Conversely, the TRG gamma were seen in germline configuration in all 19 cases of B chronic lymphoid malignancies. In none of the 9 AML cases studied was TRG gamma and TCR beta chain gene rearrangement found. The TCR beta chain genes were rearranged in one B cell chronic lymphocytic leukemia (CLL). We also show that in B-lineage ALL, the cells probably use the same V gamma genes for TRG gamma rearrangements as the malignant cells in T-ALL and the polyclonal T cells. In none of the 13 B-lineage ALL cases investigated by Northern analysis was TCR beta mRNA expression detected, whereas a weak expression of TRG gamma transcripts was found in two of these cases. The correlations between surface phenotype, rearrangement of TRG gamma, TCR beta, and Ig H chain genes were analyzed. The significance of rearrangement of TRG gamma and TCR beta chain genes in B or pre-B cells is also discussed.
D001402:B-Lymphocytes / Q000032:analysis*; D005796:Genes; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007943:Leukemia, Hairy Cell / Q000235:genetics* / Q000276:immunology; D007945:Leukemia, Lymphoid / Q000235:genetics* / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013601:T-Lymphocytes / Q000032:analysis
D007143:Immunoglobulin Heavy Chains; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta