title: FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma.
abstract: The survival of classical Hodgkin lymphoma (cHL) cells depends on activation of NF-κB, JAK/STAT, and IRF4. Whereas these factors typically induce the master regulator of plasma cell (PC) differentiation PRDM1/BLIMP-1, levels of PRDM1 remain low in cHL. FOXO1, playing a critical role in normal B-cell development, acts as a tumor suppressor in cHL, but has never been associated with induction of PC differentiation. Here we show that FOXO1 directly upregulates the full-length isoform PRDM1α in cHL cell lines. We also observed a positive correlation between FOXO1 and PRDM1 expression levels in primary Hodgkin-Reed-Sternberg cells. Further, we show that PRDM1α acts as a tumor suppressor in cHL at least partially by blocking MYC. Here we provide a link between FOXO1 repression and PRDM1α downregulation in cHL and identify PRDM1α as a tumor suppressor in cHL. The data support a potential role for FOXO transcription factors in normal PC differentiation.
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Vogel
authors.affiliation: Cancer Center of Union Hospital and.
authors.forename: Linka
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China;
authors.forename: Hanfeng
authors.initials: H
authors.lastname: Guan
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom; Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals National Health Service Trust, St. James's University Hospital, Leeds, United Kingdom;
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Tooze
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Maier
authors.affiliation: Department of Pathology and.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kostezka
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Harald J
authors.initials: HJ
authors.lastname: Maier
authors.affiliation: Genomics Core Facility, University of Ulm, Ulm, Germany;
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.affiliation: Department of Pathology and Laboratory Medicine, Centre for Lymphoid Cancers and the Centre for Translational and Applied Genomics, Vancouver, Canada;
authors.forename: Fong Chun
authors.initials: FC
authors.lastname: Chan
authors.affiliation: Department of Pathology and Laboratory Medicine, Centre for Lymphoid Cancers and the Centre for Translational and Applied Genomics, Vancouver, Canada;
authors.forename: Christian
authors.initials: C
authors.lastname: Steidl
authors.affiliation: Tri-Institutional Training Program in Computational Biology and Medicine and.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Reichel
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Clarissa D
authors.initials: CD
authors.lastname: Weitzer
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Franziska
authors.initials: F
authors.lastname: Gehringer
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Anita B
authors.initials: AB
authors.lastname: Kick
authors.affiliation: Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY; and.
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
authors.affiliation: Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY; and Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Roshal
authors.affiliation: Department of Pathology and Laboratory Medicine, Centre for Lymphoid Cancers and the Centre for Translational and Applied Genomics, Vancouver, Canada;
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.affiliation: Department of Pathology and.
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.affiliation: Institute of Physiological Chemistry, University of Ulm, Ulm, Germany;
authors.forename: Alexey
authors.initials: A
authors.lastname: Ushmorov
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1