Kai Fu, MD, PhD

University of Nebraska Medical Center, Omaha, NE

Mantle cell lymphoma (MCL) is an aggressive lymphoma characterized by a specific chromosomal translocation—a genetic event that occurs when a small piece of one chromosome switches places with a small piece of another chromosome. However, scientists have recently discovered that the translocation alone may not result in the development of MCL and that secondary alterations may play a vital role.

According to Kai Fu, MD, PhD (Associate Professor, University of Nebraska Medical Center), one of the most frequently occurring alterations targets the miR-17~92 cluster, a group of seven microRNAs (short pieces of genetic material that regulate gene expression) which are crucial for B-cell development. Previous studies have shown that higher expression of this cluster is related to poorer survival in patients with MCL.

As a result, Fu and his colleagues set out to discover the molecular mechanisms behind this negative association. “We found that higher miR-17~92 expression induces abnormal activation of a pathway in tumor cells that causes the tumor cells to become more resistant to standard chemotherapy,” says Fu.

With the Career Development Award he received from LRF, Fu will further examine the cluster’s role in the development of MCL as well as the feasibility of using the miR-17~92 cluster as a therapeutic target.

“We will conduct a pre-clinical study to determine whether suppression of miR-17~92 will improve the effect of chemotherapy, thus providing a novel approach to treat patients with this deadly disease in the future. Results from these studies will not only further our knowledge of the biology of MCL, but also promise to provide proof-of-principle data for targeting miR-17~92 in future lymphoma therapy,” says Fu.

The Millennium Pharmaceuticals, Inc./Lymphoma Research Foundation Clinical Investigator Career Development Award is supported by an independent grant from Millennium Pharmaceuticals, Inc. (Millennium). Millennium neither controlled nor influenced the nomination or selection of any award recipient.

September 23, 2009