B cells, the white blood cells that produce antibodies, form a key part
of our ‘immune response’. To remain healthy, we need to maintain the
right number of B cells, not too many and not too few. To achieve this state of homeostasis, a complex interaction of molecules within our bodies and
inside our B cells occurs.
When the B cell balance goes awry, it can result in cancers such as multiple myeloma, a disease of the bone marrow, usually requiring extensive treatment with chemotherapy and stem cell transplantation. It is often detected in the advanced stage, but diagnosis is confirmed by simple blood tests.
Recently, a multinational team of scientists have identified processes that
are heavily implicated in human multiple myeloma and other B cell
cancers. This may potentially lead to the development of quick tests that
could help in earlier diagnosis and more customised treatment of patients. Their findings were reported online in this week’s PNAS. They identified two processes that appear to
influence B cell driven cancers.
Over-expression or mutation of molecules
known as NIK and TRAF3 in B cells is associated with human multiple
myeloma. The current research found
two distinct processes involving these molecules that help explain
The first process involves NIK, an enzyme that acts closely with BAFF,
the substance that regulates the number of B cells in our bodies. Previous work by the Garvan Institute showed that levels
correlated with B cell hyperplasia (expansion) and cancer. The current
study demonstrated that if there is too much NIK in our body, then our B
cells will also expand, and we will be more susceptible to cancer.
The second process, associated with the first, involves TRAF3, the
molecule that negatively regulates NIK. In a normal person, NIK and TRAF3 work
together, helping to maintain the right number of B cells for survival. However, if there are mutations in either molecule, they become
uncoupled and TRAF 3 no longer represses the action of NIK
when necessary. When you uncouple NIK from TRAF3
action, its function will be changed. This can lead to B cell hyperplasia and
The goal in the near future is to the capacity to perform blood tests
and test for specific gene mutations in patients.
Once you identify a
mutation, you can bypass the action of that gene, with targeted
medications. Both NIK and TRAF3 are molecules, which means they can potentially be targeted by drugs. This means that new treatments for B cell cancers such as multiple myeloma may
emerge from these critical findings in the future. This is good news for patients and their advocacy groups such as the Multiple Myeloma Research Foundation.