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<p>Regulatory factor X 7 (<i>RFX7</i>) nonsense mutations have been found in different human B cell malignancies. We therefore set out to study the role of RFX7 in B cell activation and lymphomagenesis. Here we show that <i>RFX7</i> truncations cause loss-of-function and dominant-negative effects. Moreover, low <i>RFX7</i> mRNA levels correlate with worse diffuse large B cell lymphoma prognosis. Accordingly, <i>Rfx7</i> deletion in B cells accelerates pathogenesis in mouse Bcl6- and p53-loss-driven B cell lymphoma models. Rfx7-deficient B cells exhibit increased Myc activity and enhanced germinal center B cell and plasmablast responses. These alterations are reverted by Myc haploinsufficiency, which provides partial protection from nonsymptomatic <i>p53</i><sup>−/−</sup><i>Rfx7</i><sup>−/−</sup> B cell lymphoma, but does not prevent detrimental Myc deregulation in aggressive disease. Deletion of <i>Aicda</i>, which favors genomic alterations in activated B cells, limits lymphoma development in the <i>p53</i><sup>−/−</sup><i>Rfx7</i><sup>−/−</sup> double-hit mouse model. These results indicate that Rfx7 represses B cell activation, Myc activity, and Myc- and activation-induced cytidine deaminase (AID)-dependent pro-lymphomagenic processes.</p>

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Regulatory factor X 7 limits Myc activity during B cell activation and suppresses Myc-dependent lymphomagenesis

  • 期刊论文

  • 发表日期：

    2026年6月1日

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  • Berenice A. Fischer,
  • Hanif J. Khameneh,
  • Jessica Guerra,
  • Alessandro Zenobi,
  • Jasmine Ciorciari,
  • Irene Buzzago,
  • Maria Serena Merli,
  • Mohammed Said,
  • Pedro M. O. Ventura,
  • Alessandra Pfister,
  • Lara Mattei,
  • Daniele Cavalli,
  • Francesca Molinari,
  • Andrea Rinaldi,
  • Simone G. Moro,
  • Ivo Kwee,
  • Diego Morone,
  • Simone Mosole,
  • David Jarrossay,
  • Chiara Montanino,
  • Luca Simonelli,
  • Luca Varani,
  • Egle Radice,
  • Marcus Thelen,
  • Clelia Di Serio,
  • Eleonora Calabretta,
  • Margaret A. Shipp,
  • Kostantyn Dreval,
  • Ryan Morin,
  • David W. Scott,
  • Federico Jauk,
  • Milo Frattini,
  • Jessica Barizzi,
  • Luciano Cascione,
  • Francesco Bertoni,
  • Davide F. Robbiani,
  • Davide Rossi,
  • Greta Guarda

摘要

Regulatory factor X 7 (RFX7) nonsense mutations have been found in different human B cell malignancies. We therefore set out to study the role of RFX7 in B cell activation and lymphomagenesis. Here we show that RFX7 truncations cause loss-of-function and dominant-negative effects. Moreover, low RFX7 mRNA levels correlate with worse diffuse large B cell lymphoma prognosis. Accordingly, Rfx7 deletion in B cells accelerates pathogenesis in mouse Bcl6- and p53-loss-driven B cell lymphoma models. Rfx7-deficient B cells exhibit increased Myc activity and enhanced germinal center B cell and plasmablast responses. These alterations are reverted by Myc haploinsufficiency, which provides partial protection from nonsymptomatic p53−/−Rfx7−/− B cell lymphoma, but does not prevent detrimental Myc deregulation in aggressive disease. Deletion of Aicda, which favors genomic alterations in activated B cells, limits lymphoma development in the p53−/−Rfx7−/− double-hit mouse model. These results indicate that Rfx7 represses B cell activation, Myc activity, and Myc- and activation-induced cytidine deaminase (AID)-dependent pro-lymphomagenic processes.