Effects Of BCL-6 On Pathogenesis Of Non-Hodgkin's Lymphoma And The Differentiation And Apoptosis Of K562 Cells Of Leukemia

China is among the countries afflicted by high incidence of lymphomas. Of all the malignant lymphomas, non-Hodgkin's lymphoma (NHL) makes up 90 percent. However, its pathogenesis and the significantly different clinical prognosis of the same kind of NHL remain to be revealed. With the discovery of BCL-6 proto-oncogene, which as is reported, regulates lymphocyte cell fate decisions, the discovery of the pathogenesis of lymphoma is almost with our reach. Because the 5'noncoding regulatory region of BCL-6 gene is found susceptible to translocation, mutation and deletion, the change frequency was up to 87.5% in NHL. Based upon this, some researchers think that the change in the regulatory region of BCL-6 will lead to the deregulation of expression of BCL-6 protein, and hi turn, the deregulated BCL-6 might result in lymphoma. However, there are still many questions to be answered, such as whether BCL-6 gene product is expressed widely in different human normal tissues and their neoplastic counterparts as well as whether the expression level of BCL-6 must be related to changes of regulatory region of BCL-6 gene. The present study was aimed at finding answers to the above questions.In the present study, expression of BCL-6 was studied in over 10 types of human normal tissues such as lymphoid node, liver, breast, intestine, etc. andtheir neoplastic counterparts with normal immunohistochemistry. Tissues with negative result were further tested with catalyzed signal amplification (CSA) for immunohistochemistry. The result indicates that expression of BCL-6 was localized specifically in the nuclei of cells of germinal center of all reactive hyperplasia lymphoid tissue (RHL), all the follicular lymphoma (FL) and 86 percent of 29 cases of diffuse large B-cell lymphoma (DLBCL). Nevertheless, BCL-6 expression levels in different tissues differed significantly . 100 percent of 17 RLH and 77% of 13 FL cases were positive with moderate expression; 23 percent of the rest of FL cases and 72 percent of 24 positive DLBCL cases were positive with intensive expression; and BCL-6 expression was negative in all other tissues. The difference in hypermutation of the 5' noncoding region of BCL-6 gene between FLs with BCL-6 moderate expression and FLs with BCL-6 intensive expression was analyzed by using PCR, cloning and sequencing, mutations of the 5 non coding region of BCL-6 gene were found hi all 2 cases of FLs with BCL-6 intensive expression, and the changes were not found in FLs with BCL-6 moderate expression. The specific expression of BCL-6 in germinal center cells of normal lymphoid tissue may indicate the formation of the germinal center; and the mutation of regulatory region of BCL-6 gene may be the cause of intensive BCL-6 expression in a considerably small number of FLs; the intensive BCL-6 expression may be related to the pathogenesis of the relatively few FLs.Many researchers have reported that BCL-6 is closely related not only to pathogenesis of lymphoma but also to cell differentiation and apoptosis of many kinds of tumors. Expression of BCL-6 was increased when some kinds of leukemia cells were induced to differentiate. In most cases, activation of the single gene of BCL-6 induces cell differentiation or apoptosis, whereas the loss of differentiation and the apoptosis obstruction are the common characteristics of different leukemia cells. The study on how to induce leukemia cell differentiation and apoptosis and induce leukemia cells to differentiation or to apoptosis as well as the study on how to find the keygenes that respond to the differentiation and apoptosis of the induced leukemia cells are critical to a breakthrough in the therapy of leukemia.To identify the effects of BCL-6 gene on differentiation and apoptosis of induced leukemia cells, we conducted some experiments as follows.1. Three differentiation models of leukemia cell line K562 were established. HMBA (Hexamethylene Bisacetamide), TPA (0-Tetradecanoyl phorbol 13-acetate) and Hu (hydroxyurea) were selected to induce K562 cells directi...