Two Modes of DLBCL Relapse

Yanwen JiangBy Yanwen Jiang PhD 

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.

EZH2 Represents a New Target for Treatment of B-cell Lymphomas

wendybeguelinBy Wendy Béguelin, PhD

Chemotherapy for diffuse large B-cell lymphomas can have side effects and is not always effective. By targeting proteins that drive and define the lymphoma, it may be possible to reduce  our reliance on chemotherapy. Most B-cell lymphomas arise from a structure called the “germinal center” in lymph nodes. During the normal immune response, B-cells from germinal centers express high levels of proteins called BCL6 and EZH2. The combined and coordinated action of BCL6 and EZH2 can induce specific genetic changes that result in the development of malignant lymphomas. Our research, presented as 1 of 6 papers chosen from over 6,000 during the plenary session of the recent 2013 American Society of Hematology, suggests that combinations of BCL6 and EZH2 inhibitors are highly effective in destroying lymphomas and thus represent an exciting new, rationally designed treatment regimen. Fortunately, EZH2 inhibitors are already in phase I clinical trials, and specific and effective BCL6 inhibitors will be going into clinical trials.

In the Melnick Lab at Weill Cornell Medical College we are working with colleagues to develop new strategies to eradicate lymphoma and improve patient care. Please look to this space for further updates on lymphoma research in the Lymphoma Program at Weill Cornell. 

Rally for Medical Research: Help Protect Funding for Medical Research

On April 8, 2012 thousands of individuals and nearly 200 partnering programs, including representatives from the American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO), and American Association of Cancer Research (AACR) gathered at the Carnegie Library grounds in Washington, D.C. for the Rally for Medical Research. Here medical research supporters sought to raise public awareness over the importance of federally funded medical research. This need has been magnified by the March 1 sequestration mandated cuts to all areas of the federal budget, and a decade long decline in funding for the National Institute of Health (NIH).

As ASH wrote, this decline in money for medical research is not a new development:

“Research supported by the National Institutes of Health (NIH) is in serious jeopardy. NIH’s inflation-adjusted budget today is almost 20 percent lower than it was in FY 2003…Under sequestration, the NIH budget will be cut by an additional $1.6 billion over the remainder of fiscal year (FY) 2013. While the impact of these cuts may not be felt all at once or immediately, the harm caused to bio-medical research will be devastating- progress toward cures for deadly diseases and efforts to prevent costly chronic conditions will be slowed…”

Besides these  budgetary concerns, ASCO President Sandra M. Swain noted the human cost of such budget cuts, stressing the impressive strides made in cancer research due to federal funding:

“As a direct result of the federal investment in cancer research, we understand more about cancers than at any point in human history. This understanding of cancer at the molecular level has created unprecedented opportunities to slow the growth of cancer diseases. As a country, we can be proud that two of three people in the U.S. with cancer live at least 5 years after their diagnosis. This is up from one of two in the 1970s before the passage of the National Cancer Act. Since the 1990s, the nation’s cancer death rate has dropped 18 percent, reversing decades of increases. More than 13 million people in the U.S. are cancer survivors.”

Considering these new fiscal realities, the researchers and clinicians in the Lymphoma Program at Weill Cornell Medical College are adjusting accordingly. They will continue to do all that they can to deliver the latest in ground breaking research and clinical care.

Click here to use the ASH advocacy tool to contact your Representative and Senators about protecting medical research. Contact information for individual Representatives and Senators can be found here and here.