Despite improvements in care for patients with diffuse large B-cell lymphoma (DLBCL), roughly one-third of patients do not respond to initial therapy or relapse within the first 2-3 years after treatment. Unfortunately, our current understanding of the molecular mechanisms of relapse is extremely poor.
During the recent 2013 American Society of Hematology meeting, we reported for the first time that there exist at least two distinct scenarios of DLBCL relapse. In the first scenario, the tumor cells at diagnosis are almost genetically identical to tumor cells at relapse. Both tumors harbor the same set of mutations with the relapsed tumor possessing a few additional mutations, suggesting that the relapsed tumor evolved continuously from the tumor present at diagnosis. We termed this scenario “linear” mode. In the second scenario, the tumors at diagnosis and relapse carry different mutations, suggesting that an early divergent event occurred and that the tumors developed in parallel. Therefore, we named this scenario the “divergent” mode. Moreover, we observed that tumors with higher genetic heterogeneity at diagnosis were more likely to relapse through the divergent mode. This may provide a foundation for evaluation of different treatment strategies for different relapse modes.
Currently, we are expanding our study to investigate the role of epigenetics, particularly DNA methylation, in DLBCL relapse. For more research information on DLBCL, and relapsed DLBCL, please visit our websites at the Elemento Lab and the Melnick lab.