Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma

• DOI: 10.1172/jci.insight.128435
• Publication Date: 2019-08-07T15:00:57Z
• Authors: Anna K. Scherger; Mona Al-Maarri; Hans C. Maurer; Markus Schick; Sabine Maurer; Rupert Öllinger; Irene Gonzalez-Me...; Manuela Martella; Markus Thaler; Konstanze Pechloff; Katja Steiger; Sandrine Sander; Jürgen Ruland; Roland Rad; Leticia Quintanil...; Frank T. Wunderlich; Stefan Rose-John; Ulrich Keller
• Keywords: Glycoprotein 130

Aberrant activity of the glycoprotein 130 130/JAK/STAT3 (gp130/JAK/STAT3) signaling axis is a recurrent event in inflammation and cancer. In particular, it associated with wide range hematological malignancies, including multiple myeloma leukemia. Novel targeted therapies have only been successful for some subtypes these underlining need developing robust mouse models to better dissect role this pathway specific tumorigenic processes. Here, we investigated selective gp130/JAK/STAT3 activation by generating conditional model. This model constitutively active, cell-autonomous gp130 B cells, as well entire hematopoietic system. We found that regardless timing active resulted formation specifically mature cell lymphomas plasma disorders full penetrance, different latencies, where infiltrating CD138+ cells were dominant feature every tumor. Furthermore, all adult also led development largely mature, aggressive cancers, again high penetrance tumors. Importantly, abrogated differentiation block induced cell–targeted Myc transgene complete gp130-associated, CD138+, lymphoma phenotype. Thus, selectively provides strong growth advantage directs lymphomagenesis toward terminally differentiated cancers.