HODGKIN AND REED-STERNBERG CELLS DO NOT CARRY T-CELL RECEPTOR-GAMMA GENE REARRANGEMENTS - EVIDENCE FROM SINGLE-CELL POLYMERASE CHAIN-REACTION EXAMINATION

Hodgkin and Reed-Sternberg (HandRS) cells are generally accepted to be the neoplastic cells of Hodgkin's disease (HD), even though they repr esent only a minority of the cellular infiltrate in affected tissues. Recent immunologic studies and Southern blot analyses of DNA extracted from whole lymph node tissue favored, but did not convincingly prove a lymphoid origin of HandRS cells. To detect rearrangements of the T-c ell receptor gamma chain (TCR gamma) genes at the single-cell level as an indication of early T-cell lymphoid differentiation, we isolated H andRS cells by micromanipulation from cytospin preparations of fresh b iopsy material. TCR gamma chain rearrangement was detected by polymera se chain reaction using four ''forward primers'' that were constructed correspending to all four V families and two ''reverse primers'' corr esponding to consensus sequences of J segments. Rearrangements of all V families in combination with the different J segments were detected in human peripheral blood and tonsillar T cells. Although rearrangemen ts of TCR gamma chain genes were shown in single cells of 10 of 10 T-c ell leukemias, no rearrangement of these genes was found in single Han dRS cells from 13 consecutive patients with HD. Our results indicate t hat HandRS cells from the vast majority of cases are not derived from T cells. This finding may have implications for the pathogenesis of HD and the development of more effective treatment regimens. (C) 1995 by The American Society of Hematology.