Expression of the c-myc protein is down-regulated at the terminal stages during in vitro differentiation of B-type chronic lymphocytic leukemia cells.
The translocated c-myc oncogene in Burkitt's lymphoma (BL) and murine plasmacytoma (MPC) has been proposed to be expressed at a stage of differentiation at which the gene is normally silent, resulting in a continuous proliferation and an inhibited terminal differentiation. To determine whether c-myc is differently expressed at the various stages of the differentiation pathway, we used B-type chronic lymphocytic leukemia (B-CLL) cells, representing resting B lymphocytes, inducible to proliferation and/or differentiation in vitro. The c-myc protein, and Ig lambda-light chain and PCA-1 antigen as markers of B-cell maturation, were analyzed in single, morphologically defined cells by immunocytochemical double-staining. The proliferation of individual cells was determined by 3H-thymidine incorporation and by analysis of Ki-67 antigen expression. The results show that the level of c-myc expression correlates to the stage of differentiation and to the proliferative activity. Uninduced resting cells did not express c-myc. The c-myc protein was observed in the highest amount at the proliferative B-lymphoblast stage of maturation and was reduced in plasmablasts and undetectable in plasma cells. The results suggest that maturation of B cells into nonproliferative, terminally differentiated plasma cells is associated with a downregulated c-myc expression and thus support the view that the deregulated c-myc gene in BL and MPC is expressed at an inappropriate stage of maturation and thereby inhibits terminal differentiation.
Larsson
L G
LG
Department of Pathology, University of Uppsala, University Hospital, Sweden.
Schena
M
M
Carlsson
M
M
Sällström
J
J
Nilsson
K
K
D000954:Antigens, Surface / Q000032:analysis; D015152:Blotting, Northern; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D019394:Ki-67 Antigen; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008213:Lymphocyte Activation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D000954:Antigens, Surface; D004273:DNA, Neoplasm; D007146:Immunoglobulin lambda-Chains; D019394:Ki-67 Antigen; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm