| Title | FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Vogel MJ, Xie L, Guan H, Tooze RM, Maier T, Kostezka U, Maier HJ, Holzmann K, Chan FChun, Steidl C, Reichel JB, Weitzer CD, Gehringer F, Kick AB, Cesarman E, Roshal M, Gascoyne RD, Möller P, Wirth T, Ushmorov A |
| Journal | Blood |
| Volume | 124 |
| Issue | 20 |
| Pagination | 3118-29 |
| Date Published | 2014 Nov 13 |
| ISSN | 1528-0020 |
| Keywords | Cell Differentiation, Cell Line, Tumor, Down-Regulation, Forkhead Box Protein O1, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Hodgkin Disease, Humans, Plasma Cells, Positive Regulatory Domain I-Binding Factor 1, Proto-Oncogene Proteins c-myc, Reed-Sternberg Cells, Repressor Proteins, Tumor Cells, Cultured, Up-Regulation |
| 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. |
| DOI | 10.1182/blood-2014-07-590570 |
| Alternate Journal | Blood |
| PubMed ID | 25232062 |
Related Faculty:
Ethel Cesarman, M.D., Ph.D.