With this study, published in Nature Immunology, the Immune Mechanisms Laboratory, led by Greta Guarda at the Institute for Research in Biomedicine (IRB) demonstrated that the transcription factor RFX7, which is poorly studied, plays an important role in controlling B lymphocyte activation as well as the development of lymphoma. Indeed, RFX7 is often altered in human lymphomas, promoting disease progression.
Lymphoma originating from B cells, the immune cells producing antibodies to protect us from infections, remains a serious health problem despite significant treatment advances. Nowadays, we understand well the alterations of the main genes driving it, while the role of less frequently mutated genes is often neglected. RFX7 codes for a transcription factor, which limits activation and metabolic status of lymphocytes and solid tumor cell lines. Notably, multiple studies reported RFX7 alterations in human B cell malignancies; we thus set off to study the role of RFX7 in B cells and lymphoid cancer.
Our results show that Rfx7 limits B cell activation and lymphomagenesis by restraining the activity of Myc, a key transcriptional regulator of B cell proliferation, metabolism, and a known protooncogene. Moreover, we prove how alterations of RFX7 found in lymphoma can impact its transcriptional activity as well as patient clinical outcomes.
These data shed insights into the mechanisms regulating B cell activation, which might be relevant also for infection and autoimmunity. Moreover, our findings raise the possibility that MYC inhibitors, which are currently under development, might particularly benefit patients with lymphoid malignancies bearing RFX7 alterations. Altogether, our work shows how important drivers of cancer fly under the radar and how rarer mutations and unknown genes need to be studied.
This work has been a collaborative study involving researchers from Bios+ (IRB and IOR), USI, Cantonal Institute of Pathology, in Locarno, and research groups from Canada and the US.
Regulatory factor X 7 limits Myc activity during B cell activation and suppresses Myc-dependent lymphomagenesis
Fischer, B. A. Khameneh, H. J. Guerra, J. Zenobi, A. Ciorciari, J. Buzzago, I. Merli, M. S. Said, M. Ventura, P. M. O. Pfister, A. Mattei, L. Cavalli, D. Molinari, F. Rinaldi, A. Moro, S. G. Kwee, I. Morone, D. Mosole, S. Jarrossay, D. Montanino, C. Simonelli, L. Varani, L. Radice, E. Thelen, M. Di Serio, C. Calabretta, E. Shipp, M. A. Dreval, K. Morin, R. Scott, D. W. Jauk, F. Frattini, M. Barizzi, J. Cascione, L. Bertoni, F. Robbiani, D. F. Rossi, D. Guarda, G.
in Nat Immunol (2026) Vol. pp
