by Alicia Di Rado and Roberta Nichols

Sometimes medical research is a serendipitous affair. What one scientist observes and shares with colleagues can eventually unleash discoveries by other researchers many decades — or even a century — afterward.

Don Diamond, left, and Anna Israyelyan (Photo by p.cunningham)

At the turn of the 19th century, German surgeon Max Wilms, M.D., contributed so deeply to knowledge about kidney tumors that a childhood kidney cancer — Wilms’ tumor — was named after him. When researchers found that one of every five of these tumors has a mutation on a particular gene, the gene became forever tied to Wilms’ tumor. It is known as WT1.

More than a century later, scientists have come to associate that same gene and its product with a wide variety of cancers, including leukemias and breast tumors. And now, City of Hope scientists are the first to show that it may be linked to non-Hodgkin lymphoma, as well.

Sharing their results at the American Society of Hematology Annual Meeting on Dec. 13, 2011, City of Hope researchers found T cells in the blood of non-Hodgkin lymphoma patients that responded strongly to the WT1 antigen. They also found evidence that the antigen was being expressed in patients’ diseased lymph nodes, which may be the possible reservoir accounting for antigen stimulation of WT1-specific T cells.

Anna Israyelyan, Ph.D., research fellow in the lab of Don J. Diamond, Ph.D., director of the Division of Translational Vaccine Research at City of Hope, and her colleagues from the Department of Hematology & Hematopoietic Cell Transplantation, including Ryotaro Nakamura, M.D., and Stephen J. Forman, M.D., the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, presented the findings.

The researchers based their study on samples obtained from 63 patients who were enrolled in Nakamura’s research study, and pathology specimens were provided by Andreas Rosenwald, M.D., head of pathology at the University of Wurzburg Medical Center in Germany.

Interestingly, WT1 acts as a tumor suppressor for Wilms’ tumor, but promotes cancer in acute leukemias and some solid tumors.

Researchers across the world are pursuing various immunotherapy strategies targeting WT1 for cancers like leukemia. At City of Hope, the scientists plan to continue studying why non-Hodgkin lymphoma patients have WT1-reactive T cells and whether these T cells are beneficial to patients. “The potential for developing the WT1 antigen as a target for immunotherapy in non-Hodgkin lymphoma patients deserves further exploration,” Israyelyan said.

This project is supported by the Tim Nesvig Lymphoma Fellowship and Research Fund.