Live CLL Cells Inside Bone Marrow Fibroblasts May Have Implication in Drug Resistance

Lynn Wang, MD, PhD, FCAP, Professor, Medical Director of Molecular Pathology, Department of Pathology and Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, discusses live chronic lymphocytic leukemia (CLL) cells inside the bone marrow fibroblasts and their implication in drug resistance for patients with CLL. These data were presented at the 2021 Lymphoma, Leukemia & Myeloma (LL&M) Congress.

Transcript

Hi, my name is Lynn Wang. I'm an MD PhD, currently a full professor, at Fox Chase Cancer Center. I'm a board-certified pathologist, and I also have a research lab working on CLL and the non-Hodgkin lymphoma.

Basically, this is a microscopy observation we have. This particular project focuses on CLL, and under the microscope, we found some of the CLL cells getting into the bone marrow fibroblast. The bone marrow fibroblast here, were isolated from a CLL patient.

Bone marrow fibroblast serve as a part of tissue tumor microenvironment and provide growth factors for CLL to grow, but then a very interesting phenomenon we have found is that CLL cells—the tumor cells—getting to these supportive cells, the bone marrow fibroblasts.

We are very intrigued by these phenomenon’s. We did additional studies to characterize and to try to understand what this means.

This is quite new, and there is no other data leading to it. My lab has been doing CLL/lymphoma research since 2007. Basically, we were trying to build a model, build an ex vivo model, outside human body. Build a model to culture CLL cells, and let the tumor cells behave like they're in the lymph nodes. That was the initial intent of the study.

While we are building the model and trying to figure out the conditions, we observed that this interesting phenomenon that make us intrigued. We decided to continue to pursue this. In the study we have done so far, we found the number of these structures, the cell in cell, has to do with drug resistance.

We feel like these tumor cells get into the bone marrow fibroblasts, in the co-culture, with the tumor cells (the situation) is like a person seeking shelter from harmful insults. The tumor cells hide in the bone marrow fibroblast to avoid drug insult in this particular case.

Until further proven, this is a good hypothesis. All the experiments we have conducted so far support that hypothesis.

We are going to further quantify these structures, whether they really correlate with the patient clinical pathological characteristics, and then with patients, whether they receive the therapy or they have not received the therapy.

Then we're just trying to further expand our study to more cases, and then to understand what exactly this means. Although we have some indication, this are right now, at the current stage, it's considered preliminary findings, but that needs a rigorous scientific experiments to prove our hypothesis.

Then we do believe right now this structure is tumor cells seeking shelter and avoid drug treatment. If they survive drug treatment, they become residual disease, which then leads to patients' disease relapse. I think the clinical implication is huge, but we need some hard evidence to support and to prove that's the case.

My laboratory has been working on CLL and non-Hodgkin lymphoma between 15 and 20 years.

Our lab is one of the first to identify the mechanism for ibrutinib resistance. That study published in New England Journal of Medicine.

Since that, the lab has been focused on the drug-sensitive and resistant mechanisms, and trying to identify biomarkers to predict sensitivity or resistance to a certain drug in CLL and the non-Hodgkin lymphoma.

This has helped us to deliver personalized therapy for patients. The biomarker will identify the disease in a particular way, and then identify whether these subpopulations of patients are either sensitive, will benefit from the treatment, or resistant, will unlikely benefit from the treatment. That's the goal, and that's our work, what we've been working on.