The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma

Hodgkindisease (HD) is characterized by a small numberofputativemalignant cells [HodgkinandReed-Sternberg (HRS) cells] among a background of lymphocytesandhistiocytes. The lineage ofHRS cells is still elusive anda clonal origin of these rare cells hasnot formally been demon-strated. Weisolated HRScells by micromanipulation fromhistologicalsectionsofthreecasesofHodgkinlymphoma(eachrepresenting a distinct subtype of the disease) and analyzedindividual cells for immunoglobulin variable (V) gene rear- rangements by PCR. In each of the three cases a singieheavy-chain V (VH) (and in one case, in addition, a K light-chain)generearrangement was amplifiedfromtheHRScells, identifying these cells as membersof a single done. A poten-tiallyfunctionalVHrearrangement was obtainedfrom acase ofnodular sclerosis HD. Somatic mutations and intraclonal di- versity in the VHgenesindicate a germinal center B-cell originof the HRScells in a case of lymphocyte-predominant HD,whereas ina caseof mixed-cellularity

Hodgkin disease: Hodgkin andReed-Sternberg cells picked from histological sections showclonal immunoglobulin gene rearrangements andappear tobederived fromB cells atvarious stages ofdevelopment

Epstein-Barr virus (EBV) is an extremely successful virus, infecting more than 90% of the human population worldwide. After primary infection, the virus persists for the life of the host, usually as a harmless passenger residing in B cells. However, EBV can transform B cells, which can result in the development of malignant lymphomas. Intriguingly, the three main types of EBV-associated B-cell lymphoma - that is, Burkitt lymphoma, Hodgkin lymphoma and post-transplant lymphomas - seem to derive from germinal-centre B cells or atypical survivors of the germinal-centre reaction in most, if not all, cases, indicating that EBV-infected germinal-centre B cells are at particular risk for malignant transformation.

B cells under influence: transformation of B cells by Epstein–Barr virus

The role of cytokines in classical Hodgkin lymphoma

Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma

Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription

Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells

gene rearrangements but defective immunoglobulin transcription originating from a germinal center B-cell with functional immunoglobulin Hodgkin and Reed-Sternberg cells represent an expansion of a single clone

Jan Theil

Papers

Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription

Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells

gene rearrangements but defective immunoglobulin transcription originating from a germinal center B-cell with functional immunoglobulin Hodgkin and Reed-Sternberg cells represent an expansion of a single clone