Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells.
A novel Hodgkin's disease (HD) derived cell line, L1236, was established from the peripheral blood of a patient with advanced Hodgkin's disease. Analysis of immunoglobulin (Ig) gene rearrangements revealed a biallelic Ig heavy chain and a monoallelic Ig kappa light chain gene rearrangement, pointing to a B-lymphoid origin of these cells. No DNA of Epstein-Barr virus was detected in L1236. The cells expressed the HD-associated surface antigens CD30 and CD15 as well as the transferrin receptor (CD71). Cytogenetic analysis of early passages of L1236 cells revealed a grossly disordered karyotype including cytogenetic aberrations described previously in other HD-derived cell lines. The Hodgkin/Reed-Sternberg (H-RS) cell origin of L1236 cells is further confirmed by Kanzler et al (Blood 87:3429, 1996), who found identical Ig gene rearrangement sequences in L1236 cells and H-RS cells of the same patient's bone marrow. L1236 cells expressed antigens necessary for efficient antigen presentation to T cells including HLA class I and II, B7.1 and B7.2, as well as adhesion molecules ICAM 1 and LFA 3. The cells secreted the interleukins (IL)-6, -8, -10, tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, transforming growth factor (TGF) beta, and the granulocyte-macrophage colony stimulating factor (GM-CSF). After subcutaneous inoculation into SCID mice, a necrotic regression of initially growing tumors at the injection site was followed by disseminated intralymphatic growth. Our findings, together with the results of Kanzler et al, demonstrate that H-RS cells of B-lymphoid origin were present in the peripheral blood of a patient with advanced HD. These cells exerted a malignant phenotype with regard to their in vitro and in vivo characteristics.
Wolf
J
J
Department of Internal Medicine I, Universität zu Köln, Germany.
Kapp
U
U
Bohlen
H
H
Kornacker
M
M
Schoch
C
C
Stahl
B
B
Mücke
S
S
von Kalle
C
C
Fonatsch
C
C
Schaefer
H E
HE
Hansmann
M L
ML
Diehl
V
V
D000328:Adult; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis; D001402:B-Lymphocytes / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D017809:Fatal Outcome; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006689:Hodgkin Disease / Q000097:blood* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000032:analysis; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016207:Cytokines; D009363:Neoplasm Proteins