THE PROTOONCOGENE C-FGR IS EXPRESSED IN NORMAL MANTLE ZONE B-LYMPHOCYTES AND IS DEVELOPMENTALLY-REGULATED DURING MYELOMONOCYTIC DIFFERENTIATION IN-VIVO

The proto-oncogene c-fgr is a member of the c-src gene family of cytop lasmic tyrosine kinases. Previous studies have suggested that it is no rmally expressed in neutrophils, monocytes, macrophages, and natural k iller cells. c-fgr is also expressed in the B cells of certain lymphop roliferative disorders, namely, Epstein-Barr virus-associated lymphopr oliferative disease, and in chronic lymphocytic leukemia, but it has n ot previously been detected in normal or reactive human lymphoid tissu e. In this study we have determined the pattern of p55(c-fgr) protein expression in normal human hematopoietic and lymphoid tissues at the s ingle-cell level using immunohistochemical and immunofluorescent techn iques. We show that p55(c-fgr) expression is developmentally regulated with high-level expression first evident at the myelocyte stage of my eloid differentiation. In addition, we show that p55(c-fgr) is express ed in circulating B lymphocytes isolated from chronic lymphocytic leuk emia patients but is not expressed in normal circulating B lymphocytes . Surprisingly, p55(c-fgr) is also expressed in a subpopulation of nor mal B lymphocytes, the mantle zone B lymphocytes. This demonstration t hat p55(c-fgr) is expressed in a normal B-lymphocyte subpopulation sug gests that its expression in certain B-cell lymphoproliferative disord ers may be an indirect consequence of, rather than a primary cause of, the neoplastic transformation process. (C) 1995 by The American Socie ty of Hematology.