Targeting lyphoma's command center

BACKGROUND:   Lymphoma is the most common blood cancer.  The two main forms are Hodgkin lymphoma and non-Hodgkin lymphoma.  Lymphoma occurs when white blood cells, lymphocytes, grow abnormally.  The body has two main type of lymphocytes that can develop into lymphomas, B-lymphocytes (B-cells) and T-lymphocytes (T-cells).  The cancerous lymphocytes can travel to any different parts of the body, including the lymph nodes, bone marrow, spleen, blood, other organs, and can form tumors.  Non-Hodgkin lymphoma (NHL) is the most common lymphoma cancer.  Incidence rates for NHL have almost doubled since the 1970s.  Of the 500,000 Americans who have lymphoma, around 332,000 have NHL.  NHL is not a single disease.  It is a group of several closely related cancers.  The World Health Organization estimates 61 different types of NHL.  (Source: www.lymphoma.org)


SYMPTOMS:  Common symptoms of NHL include swelling of the lymph nodes, fever, night sweats, lack of energy, and unexplained weight loss.  The causes of NHL are unknown, but risks include:  a family history, affected with an autoimmune disease, have received an organ transplant, have been infected with viruses like AIDS or Hepatitis C, or have been exposed to chemicals like pesticides.   (Source: www.lymphoma.org)


STAGES:  NHL is divided into four stages: 

Stage I (early disease): The cancer is only in one lymph node, in one organ, or in an area outside the lymph node.

Stage II (locally advanced disease):The cancer is found in two or more lymph node regions on one side of the diaphragm.

Stage III (advanced disease):The cancer involves lymph nodes above and below the diaphragm.

Stage IV (widespread disease):The cancer is found in several parts of one or more organs or tissues (in addition to the lymph nodes), in the liver, blood, or bone marrow. (Source: www.lymphoma.org)


NEW TECHNOLOGY:  Treatment options can include:  watchful waiting, radiation therapy, novel targeted agents, stem cell transplantation, or chemotherapy.  However, there is a certain subtype of Non-Hodgkin's lymphoma that is resistant to chemotherapy, called activated B-cell-DLBCL (diffuse large B-cell lymphoma).  An international effort discovered the experimental molecule agent, MI-2, that inactivates the key protein that is responsible for the growth and survival of activated B-cell-DLBCL, known as MALT1.  Researchers say that a single drug cannot cure lymphoma, which is why they need to combine agents that can kill the different cellular pathways that lymphoma cells use to survive.  They believe that the use of chemotherapy is too toxic and needs to be eliminated in treating lymphoma and the discovery of MI-2 will bring them closer to creating a combination of molecular targeted therapy regimens.  MALT1 is the only paracaspase that is produced in humans and it is a particular protein that can rip apart other proteins.  So, when MALT1 cuts proteins in activated B-cell-DLBCLs, it can activate growth and can stop other proteins from inhibiting that growth.  When the researchers tested MI-2 in mice, they found that it had stopped the growth of cancer and did it without toxicity in normal tissues.  Researchers believe that if MI-2 is successful in human clinical trials, then it could play a role in other diseases, including MALT1 lymphoma (a lower-grade type of lymphoma).  It could also be beneficial for a variety of inflammatory and autoimmune diseases. (Source: http://weill.cornell.edu/news/releases/wcmc/wcmc_2012/12_10_12-2.shtml)


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Lauren Woods

Senior Media Associate

Weill Cornell Medical College

(646) 317-7401