Transcription Factors

You are here:

The role of B-cell specific transcription factors in Hodgkin lymphoma

PAX5 is a transcription factor, expressed during most stages of B-cell differentiation and down-regulated during plasma cell development. In turn, the transcription factor IRF4 is being up-regulated during plasma cell differentiation. The co-expression of both transcription factors is not found in normal B- or plasma cells but is observed in more than 90% of classical Hodgkin lymphomas (cHL) and approximately 50% of diffuse large B-cell lymphomas (DLBCL), although both lymphomas show a completely different phenotype.

We examine the genome-wide binding profile and function of PAX5 and IRF4 in cHL and DLBCL cell lines. Our aim is not only to determine new target genes of both transcription factors, but also to resolve why PAX5 is not able to restore the B-cell phenotype in cHL and which role IRF4 plays during plasma cell differentiation.

Literature

Dimitrova L, Seitz V, Hecht J, Hansen P, Szczepanowski M, Ma L, Oker E, Sommerfeld A, Jundt F, Klapper W, Hummel M. PAX5 overexpression is not enough to reestablish the mature B-cell phenotype in classical Hodgkin lymphoma. Leukemia. 2014 Jan;28(1):213-6. Epub 2013 Jul 11.  http://www.ncbi.nlm.nih.gov/pubmed/18256685PMID: 23842424

Ehlers A, Oker E, Bentink S, Lenze D, Stein H, Hummel M. Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype. Leukemia. 2008 Apr;22(4):835-41. Epub 2008 Feb 7. PMID: 18256685

Marafioti T, Hummel M, Foss HD, Laumen H, Korbjuhn P, Anagnostopoulos I, Lammert H, Demel G, Theil J, Wirth T, Stein H. 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. Blood. 2000 Feb 15;95(4):1443-50. PMID: 10666223

Supported by SFB/Transregio 54 "Wachstum und Überleben, Plastizität und zelluläre Interaktivität lymphatischer Neoplasien"