Optimal Therapeutic Management of Mantle Cell Lymphoma - Episode 2

Biology of Mantle Cell Lymphoma


Brad Kahl, MD: Mantle cell lymphoma has a unique biology, unlike any other lymphoma subtype, and it’s characterized by overexpression of cyclin-D1. Cyclin-D1 overexpression results in abnormal proliferation of mantle cells through the cell cycle and is really the hallmark of this disease, and it’s 1 of the features we use to diagnose mantle cell lymphoma. But from mouse models, we know that cyclin-D1 overexpression, which is a result of an 11;14 translocation, is not enough to cause mantle cell lymphoma. That is probably the first hit, or at least a very early hit, in the pathogenesis of mantle cell lymphoma, and then downstream events lead to the full-blown development of mantle cell lymphoma. There are other mutations in genes that are very common, such as the ATM gene, in mantle cell lymphoma.

We know that there is a lot of biologic heterogeneity in mantle cell lymphoma. When patients acquire mutations in p53, when patients acquire a complex karyotype—meaning they’re really starting to accumulate secondary genetic events—the prognosis for mantle cell lymphoma gets much worse, and those patients become particularly difficult to manage.

Mantle cell lymphoma can present like other lymphoid malignancies. Patients might present with simple lymphadenopathy, and so that could be the presentation for any other type of lymphoma. Patients can present with splenomegaly and peripheral blood lymphocytosis, and so it can mimic chronic lymphocytic leukemia, hairy cell leukemia, and splenic marginal zone lymphoma. So, there is a variety of other lymphoid malignancies that have to be considered along with mantle cell lymphoma when a patient comes in with that clinical picture.

We use the Ann Arbor staging system for mantle cell lymphoma, which is the system we use with most lymphomas. It turns out that most mantle cell lymphoma patients have Ann Arbor stage 3 or 4 disease just because of the biology of mantle cell lymphoma. Most patients have the disease very widespread at the time of diagnosis, so we typically find it in multiple nodal regions. We often find it in extranodal sites. It’s very common to find it in the GI tract, and it’s very common to find it in the blood and in the bone marrow.

Transcript Edited for Clarity