Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells

Abstract

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.

The landscape of somatic mutation in normal colorectal epithelial cells

“…This individual had been treated with multiple chemotherapeutic agents (including cyclophosphamide, doxorubicin, vincristine, prednisolone, chlorambucil, bleomycin and etoposide) for lymphoma and subsequently developed caecal adenocarcinoma. SBSD resembles SBS25, (cosine similarity 0.9), previously found in Hodgkin lymphoma cell lines from two chemotherapy–treated patients 31,37 . To our knowledge this is the first time that the mutational consequences of chemotherapy have been demonstrated in normal human cells in vivo .…”

Proficient mismatch repair protein expression in Hodgkin and Reed Sternberg cells

“…From the immunohistochemistry, it is thus concluded that (i) H/RS cells are proficient for hMSH2 and hMLH1 protein expression, (ii) genes encoding for hMSH2 and hMLH1 most probably are in wild-type configuration, and (iii) H/RS cells are unlikely to be MSI-high. This is conceivable with the results from our single cell study showing absence of MSI in H/RS cells in seven cases (cases [21][22][23][24][25][26][27].…”

“…The Epstein-Barr virus negative H/RS cell line L1236 was established at our institution. 25 Clonal derivation of L1236 cells from H/RS cells of the patient was demonstrated by amplification of identical Ig gene rearrangements from both sources. 26 Cells were cultured under standard conditions.…”

Deregulation of immunoglobulin gene transcription in the Hodgkin–Reed Sternberg cell line L1236

“…Cell lines. H-RS cell line L1236 (Wolf et al, 1996), B-cell lymphoma line BJA-B and NIH3T3 fibroblasts were grown according to standard conditions.…”