Rearrangement of Variable Region T Cell Receptor y Genes in Acute Lymphoblastic Leukemia Vy Gene Usage Differs in Mature and Immature T Cells

Using probes recognizing variable regions (V gamma) and joining regions (J gamma) of the T cell receptor (TCR) gamma gene, we have analyzed the usage of V gamma genes in 24 patients with T cell acute lymphoblastic leukemia (ALL) and 36 patients with B-precursor ALL. In CD3- T-ALL derived from immature T cells, V gamma genes more proximal to J gamma were frequently rearranged; V gamma 8, V gamma 9, V gamma 10, and V gamma 11 were used in 19 of 24 rearrangements. In contrast, CD3+ T-ALL derived from a more mature stage of T cell ontogeny, showed a high frequency of rearrangements involving V gamma genes distal to J gamma; V gamma 2, V gamma 3, V gamma 4, and V gamma 5 were used in 17 of 25 rearrangements. In B-precursor ALL, no notable bias of V gamma gene usage was observed. This probably reflects the possibility that TCR genes may not rearrange according to a T cell hierarchy when under control of a B cell gene program. Furthermore, deletions of those V gamma genes located 3' to rearranged V gamma genes were observed in all patients analyzed. This supports the theory that loop deletion is a major mechanism for TCR-gamma gene rearrangement

Rapid Publication Immunoglobulin,-Chain Gene Rearrangement in a Patient with T Cell Acute Lymphoblastic Leukemia

Abstract. A 6-yr-old girl with T cell acute lymphoblastic leukemia (ALL) is described. She had a mediastinal mass and her leukemic cells expressed T cellassociated antigens (Leu 1+, OKT3+, OKT9+, and OKTIO+). When we examined genomic DNA from the leukemic cells, we detected Ig M-chain gene rearrangement with germ-line configuration of light chain genes. As reported recently, detecting Ig gene rearrangement has become an important procedure for further classifying B cell precursor cells. This case, however, suggests that there is also heterogeneity among patients with T cell ALL, not only at the level of cell surface phenotypes, but also at the level of the Ig gene. These findings have major implications when we consider both the ontogenesis of these leukemic cells and the normal differentiation of human lymphocytes