NIH Distinguished Investigator Discusses the Evolution of Lymphoma Classification

Pharmacy Times interviewed Elaine Jaffe, MD, National Institutes of Health (NIH) distinguished investigator at the National Cancer Institute at NIH, who is receiving the American Society for Investigative Pathology Gold-Headed Cane Award and is presenting an award lecture at the Experimental Biology 2022 conference on the classification of lymphoma in the modern era—a marriage of pathology and genomics.

During this interview, Jaffe discussed points of note in the evolution of lymphoma classification during her clinical and investigational research on the subject.

Elaine Jaffe: Well, I mean, I think there were 2 areas that I was involved in, and that I think were important advances. One nearly 20 years ago, we described insight to follicular lymphoma. This was really the earliest event in the molecular evolution of follicular lymphoma associated with the BCL2 translocation, but most of the people who had this so-called insight to follicular lymphoma, never developed follicular lymphoma.

We know that if you look carefully with sensitive genetic tools at individuals over the age of 50, 70% of them carry B cells with the BCL2 translocation. So we now know a lot more about that phenomenon. These very early cells that carry the BCL2 translocation that are found in normal individuals are considered clonal progenitors, and they're an essential component of the ultimate evolution towards lymphoma. Even if they're not malignant themselves. We see that these cells can evolve by branching evolution, and that has helped us to understand many of the key events that predict eventual evolution to lymphoma with acquired secondary genetic changes.

Another area that I was involved in was the demonstration of lineage plasticity. We used to think that once the cell matures into a B cell, T cell, or histiocyte, it's frozen in that lineage. But we've begun to appreciate lineage plasticity within many neoplasms.

So, for example, going back to follicular lymphoma, we've seen the acidic sarcomas develop in patients with follicular lymphoma and have been able to show that those history acidic sarcomas have immunoglobulin gene rearrangement. So at the genetic level, they should be B cells, and they carry the BCL2 translocation, but the clonogenic precursors can undergo lineage switch and manifest different lineage characteristics, and we've seen this both in B cell and T cell neoplasms.