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Different T-Cell Receptor Gene Configurations in T-Cell Neoplasms and Acute Lymphoblastic Leukemia¹

Hematology/Oncology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Southern blotting and multiple restriction enzymes were used to analyze T-cell receptor (TCR) and immunoglobulin heavy chain genes in 20 postthymic T-cell neoplasms, ten prethymic and thymic T-cell tumors, and 45 cases of precursor-B acute lymphoblastic leukemia (ALL). Immunoglobulin heavy chain, never rearranged in a postthymic specimen and only once in a prethymic/thymic sample, was rearranged in all but two cases of precursor-B ALL. In contrast, biallelic rearrangement of TCR_ß with deletion of the first constant region germline fragment was regularly seen in T-cell neoplasms, but only twice in the 45 precursor-B ALL cases. TCR, was rearranged in all but one postthymic sample, in all prethymic/thymic samples, and in approximately half of precursor-B ALL specimens as well. Preferential use of V regions was evident among the various disorders: V8 and V10 in postthymic neoplasms; and V3, V5, V7, and, particularly, V9 in precursor-B ALL. In all the studied conditions, TCR was rarely in germline configuration. Extensive biallelic deletion of J1, J2, and C, almost always (19 of 20 specimens) present in postthymic neoplasms, was observed in only a minority (14 of 45) of precursor-B ALL samples. In precursor-B ALL, rearranged antigen receptor genes were more frequently found in common acute lymphoblastic leukemia antigen-positive and terminal deoxynucleotidyl transferase-positive specimens. Furthermore, TCR gene rearrangement in that disorder was characterized by a hierarchical pattern: TCR_ß was not rearranged without TCR nor TCR without TCR. Despite uncertainty of the mechanism, the various disorders can be distinguished on the basis of characteristic antigen receptor gene patterns.

¹ This work was supported by Grant CA 30020 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Massachusetts General Hospital, Fruit Street, Boston, MA 02114.

Received 6/12/91. Accepted 9/10/91.