T-CELL DIFFERENTIATION STAGES IDENTIFIED BY MOLECULAR AND IMMUNOLOGICAL ANALYSIS OF THE T-CELL RECEPTOR COMPLEX IN CHILDHOOD LYMPHOBLASTIC-LEUKEMIA

  • 1 March 1987
    • journal article
    • research article
    • Vol. 69  (3) , 908-912
Abstract
T cell differentiation was investigated by determining the relationship of T cell receptor (Ti) gene rearrangement and transcription to the expression of surface and cytoplasmic T3 antigen using blast cells from five children with acute lymphoblastic leukemia of thymic origin. Patterns of monoclonal antibody (MoAb) reactivity indicated that these cases were representative of the three recognized stages (I, II, III) of human thymocyte development. The T3 antigen, which becomes linked to the Ti to form a functional T cell receptor complex on mature thymocytes, was expressed on the cell surface in two cases (stage III). However, in the remaining three cases that were surface T3 negative (stages I and II), large amounts of T3 were identified in the cytoplasm by immunoperoxidase staining and flow cytometry. Leukemic blasts from all five patients showed rearranged genes encoding the .beta.-chains portion of the Ti heterodimer. RNA transcripts of Ti .beta.-chain genes were also evident in lymphoblasts from all five cases, but transcripts coding for the .alpha.-chain portion of Ti were found only in cases that expressed T3 on the cell surface. Thus, the absence of surface T3 (and presumably Ti) coincides with the absence of Ti .alpha.-chain RNA, suggesting that transcription of .alpha.-chain genes is a critical regulatory event in the surface expression of the Ti-T3 complex. Leukemic T cells that rearrange and express Ti .beta.-chain genes but lack Ti .alpha.-chain messenger RNA (mRNA) may represent a stage of differentiation analogous to pre-B cells, where heavy-chain immunoglobulin (Ig) genes are rearranged and expressed but light-chain Ig genes are not expressed.