Citations 2
Malignant B-cell States Orchestrate Spatially Organized Immune Ecosystems in B-cell Lymphomas
Mondello, Patrizia , Sadekova, Alisa , fede, ksenia, Dasari, Surendra , Au, Wesley , Kriukov, Kirill , Meerson, Mark, Novak, Joseph, Yang, Zhi-Zhang , Gysbers, Brianna J. , Villasboas, Jose, Wiebe, Daniil S. , Shvyrkova, Anastasiia, Margaryan, Sargis, Nesmelov, Alexander, Sarachakov, Aleksander, Petrosyants, Arman, Bagaev, Alexander , Novak, Anne J. , Casulo, Carla, Hsi, Eric, Fowler, Nathan, King, Rebecca, Singh, Harinder, Armand, Philippe, Pasqualucci, Laura, Ansell, Stephen M. , Binder, Moritz , Yang, Zhi-Zhang , Gysbers, Brianna J , Postovalova, Ekaterina , Wiebe, Daniil , Kotlov, Nikita , Wang, Yucai , Novak, Anne J , Habermann, Thomas , Maurer, Matthew , Cerhan, James R , Shlomchik, Mark , Ansell, Stephen M , Mondello, Patrizia , Dasari, Surendra , Au, Wesley, Binder, Moritz , Meerson, Mark , Novak, Joseph P. , Villasboas, José C. , Guzman, Emmanuel Contreras , Nesmelov, Alexander, Wang, Yucai , Habermann, Thomas M. , Hsi, Eric D. , Maurer, Matthew J. , Cerhan, James R. , Singh, Harinder, Armand, P., Pasqualucci, Laura , Burack, Richard
No container title available | August 3, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Germinal center (GC)-derived lymphomas arise within a specialized immune ecosystem, yet whether malignant cells direct its remodeling remains unclear. Integrating genomic, transcriptomic, spatial, and functional analyses across follicular lymphoma and diffuse large B-cell lymphoma, we define a developmental framework linking malignant B-cell differentiation state to tumor microenvironment (TME) organization. Rather than segregating by histology, lymphomas align along a shared differentiation continuum in which proliferative dark zone (DZ) states associate with immune-depleted TMEs, whereas post-GC/memory B-cell (MBC) states drive inflamed but immunosuppressed TMEs. Spatial profiling reveals collapse of GC architecture and emergence of suppressive myeloid niches along this trajectory. Single-cell lineage reconstruction uncovers a DZ-to-MBC developmental axis underlying lymphoma evolution. Genetic reprogramming in vivo demonstrates that malignant differentiation state is sufficient to instruct TME remodeling. Collectively, these findings establish malignant differentiation state as a causal determinant of immune architecture across GC-derived lymphomas and identify lineage-directed immune reprogramming as a potential therapeutic strategy.
Survival Trends in Waldenström Macroglobulinemia and Comparison of Outcomes with the General US Population
Zanwar, Saurabh , Khan, Muhammad Azeem , Gaur, Gunjan , Abeykoon, Jithma P. , Gertz, Morie A. , Kumar, Shaji , King, Rebecca, Habermann, Thomas M. , Go, Ronald S. , Abdallah, Nadine , Thanarajasingam, Gita , Thompson, CM, Nowakowski, Grzegorz S. , Dasari, Surendra , Novak, Joseph, Warsame, R., Ansell, Stephen M. , Kapoor, Prashant , Go, Ronald S , Gertz, Morie A , Habermann, Thomas , Paludo, Jonas , Cook, Joselle , Buadi, Francis K. , Dispenzieri, Angela , Gonsalves, Wilson I. , Dingli, David , Muchtar, Eli , Greipp, Patricia T. , Novak, Joseph P. , Warsame, Rahma , Witzig, Thomas E. , Rajkumar, S. Vincent
No container title available | June 17, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Therapeutic options for Waldenström macroglobulinemia (WM) have expanded but improvements in overall-survival (OS) are difficult to interpret due to competing non–WM mortality. We conducted a large single-center retrospective study of 1,020 patients with WM to evaluate survival trends. Patients were stratified by era of active WM diagnosis using a two-era model (1996–2005 and post-2005) and a four-era model (pre-2001, 2001–2007, 2008–2013, and post-2013). OS did not differ significantly across eras in the overall cohort (p = 0.64 and p = 0.86 for the two- and four-era models). However, among patients aged < 65 years at the time of active WM diagnosis in the 2-era model, OS improved in the post-2006 era (median 18.8 vs 14.1 years, p = 0.018). Cause-specific-survival (CSS) improved across all eras, increasing from 15.6 years in 1996–2005 to 18.9 years post-2006 (p < 0.0001), and from 13.7 years pre-2001 to not reached in later periods in the four-era model (p < 0.0001). Competing-risk-analysis (CRA) demonstrated a reduction in WM-related mortality over time (p < 0.001). However, excess mortality persisted, with a standardized mortality ratio (SMR) of 2.79 (p < 0.001) among patients < 65 years compared with a matched U.S. population. Our findings highlight improvements in WM-specific survival, while gains in OS are observed in younger patients.