No abstract

Relapses are observed in the majority of patients, in some cases additionally associated with transformation to more aggressive diffuse large B-cell lymphoma. Data of paired primary and relapsed t(14;18) positive FL revealed a large evolutionary heterogeneity, ranging from "divergent evolution" (primary and relapse tumors arise from a common precursor), to "sequential" (relapse sequences emerge out of primary clones) and "no evolution" (shared IGHV sequences in primary and relapse tumors). In order to gain insight into processes underlying clonal evolution and lymphoma relapse, we applied a mathematical modeling approach. We particularly sought to conclusively explain Conclusions:We found a comprehensive mathematical model of physiological GC reaction, dynamics of FL emergence and heterogeneity of clonal evolution. Due to the stochasticity of evolution we caution to draw clinically relevant conclusions from evolutionary profiles of tumor cells (e.g., with respect to transformation). Suppression of interfollicular cell migration through lymphatic vessels already in early disease stages might be a therapeutic goal.