FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma.

نویسندگان

  • Marion J Vogel
  • Linka Xie
  • Hanfeng Guan
  • Reuben M Tooze
  • Thomas Maier
  • Ulrike Kostezka
  • Harald J Maier
  • Karlheinz Holzmann
  • Fong Chun Chan
  • Christian Steidl
  • Jonathan B Reichel
  • Clarissa D Weitzer
  • Franziska Gehringer
  • Anita B Kick
  • Ethel Cesarman
  • Mikhail Roshal
  • Randy D Gascoyne
  • Peter Möller
  • Thomas Wirth
  • Alexey Ushmorov
چکیده

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.

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عنوان ژورنال:
  • Blood

دوره 124 20  شماره 

صفحات  -

تاریخ انتشار 2014