HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma

Roberta Zappasodi, Giusi Ruggiero, Carla Guarnotta, Monica Tortoreto, Cristina Tringali, Alessandra Cavanè, Antonello D. Cabras, Lorenzo Castagnoli, Bruno Venerando, Nadia Zaffaroni, Alessandro M. Gianni, Filippo De Braud, Claudio Tripodo, Serenella M. Pupa, Massimo Di Nicola

Research output: Contribution to journalArticle

Abstract

We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and primary aggressive B-NHLs. Accordingly, expression of HSPH1 and either c-Myc or Bcl-6 positively correlated in these diseases. Our study indicates that HSPH1 concurrently favors the expression of 2 key lymphoma oncoproteins, thus confirming its candidacy as a valuable therapeutic target of aggressive B-NHLs.

Original languageEnglish
Pages (from-to)1768-1771
Number of pages4
JournalBlood
Volume125
Issue number11
DOIs
Publication statusPublished - Mar 12 2015

ASJC Scopus subject areas

  • Medicine(all)

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