Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulintranscription

In contrast to the tumor cells (L&H cells) of lymphocyte predominant Hodgki n disease (LPHD), Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgk in disease (cHD) are unable to transcribe immunoglobulin, despite the prese nce of rearranged immunoglobulin genes. Although initial studies have sugge sted crippling immunoglobulin gene mutations to be the cause of absent immu no-globulin expression in cHD, recent work of our group has demonstrated an impaired activation of the immunoglobulin promoter as a superior mechanism , As immunoglobulin transcription is mainly regulated by the B-cell transcr iption factors Oct2 and BOB.1/OBF.1, we analyzed 35 cases of LPHD, 32 cases of cHD, and 2 Hodgkin disease cell lines for the expression of these trans cription factors and also in parallel for immunoglobulin expression. Our re sults demonstrate an absence of Oct2 and/or BOB.1/OBF.1 in cHD and a striki ng overexpression of Oct2 in LPHD. Immunoglobulin expression was lacking in cHD but present in LPHD. Furthermore, the reintroduction of BOB.1/OBF.1 an d Oct2 into cultured HRS cells restored the activity of cotransduced immuno globulin promoter constructs. Our findings dismiss the concept that the dif ferent immunoglobulin expression in cHD and LPHD is due to disrupting mutat ions of immunoglobulin V genes in cHD but is most likely due to a down-regu lation of Oct2 and/or BOB.1/OBF.1. This study further revealed Oct2 as a ne w and valuable marker for the identification of L&H cells and their distinc tion from HRS cells, The impairment of immunoglobulin transcription with a down-regulated synthesis of Oct2 and BOB.1/OBF.1 is the first established g eneral recurrent defect found in HRS cells. (C) 2001 by The American Societ y of Hematology.