We’re pleased to highlight a research study led by Dr. Nina Rolf, a clinician scientist in Dr. Gregor Reid’s Lab, in collaboration with Dr. Suzanne Vercauteren and colleagues.
A Clinical & Translational Research Seed grant awarded to Dr. Nina Rolf paved the way for a new collaborative study with Dr. Vercauteren’s team at BC Children’s Hospital. In a recent publication in Cytometry Part A, the team presented a new methodology for investigating whether xenotransplants from primary leukemia cells of acute lymphoblastic leukemia (ALL) patients display identical immunological marker profiles as the cancer cells in a patient. ALL is a type of blood cancer that originates in white blood cells and is the most common type of cancer in children.
Although survival rates of children with leukemia have significantly increased in recent decades, relapsed leukemia still remains challenging to cure. Since patient-derived leukemic cells do not survive long-term in vitro, in recent years researchers have used models where tumour cells are taken from a patient and then implanted into immunosuppressed mice, known as a PDX (patient-derived xenografts)-based cancer model. At BC Children’s, primary samples can be used from the BC Children’s Hospital BioBank to study the biology of this disease as well as the response to novel therapeutic approaches.
ALL-PDX models have shown significant potential as screening platforms for clinical trials and personalized medicine. However, their utility depends on their ability to accurately model clinical disease.
The immunophenotype of a patient’s leukemia is usually assumed to remain stable in PDX mice, but there is a lack of in-depth comparative studies to confirm this. When children with ALL are treated in the hospital, their treatment is heavily reliant on the use of flow cytometry to identify leukemic cells from normal bone marrow cells. This is done by distinguishing their complex leukemia-associated immunophenotypic pattern (LAIP). In clinical flow diagnostics, using rigorously standardized flow protocols is essential as there is significant heterogeneity of the LAIP between patients and during disease progression.
The development of a translational flow cytometry platform
Due to the Reid Lab’s expertise in this area, ALL-PDX models have become an integral component of the BRAvE (Better Responses through Avatomics Evidence) Precision Medicine Program of the Michael Cuccione Childhood Cancer Research Program, which includes the research teams of Dr. Chris Maxwell, Dr. James Lim, Dr. Philipp Lange and Dr. Gregor Reid.
By integrating their unique areas of expertise into one streamlined approach, these research teams developed a translational flow cytometry platform that can determine the immunophenotypic accuracy between the patient’s leukemia and the patient-derived xenografts (PDX). In addition, by using an algorithm-based high-dimensional flow analysis, this platform can help translational researchers examine the phenotypic subpopulation complexity of childhood ALL for each patient, which in the future could influence clinical therapy response assessment.
How did Core Technologies & Services support this research?
Lorraine Liu manages the clinical flow core at the Division of Pediatric Hematopathology at BC Children’s, and together with division head Dr. Vercauteren and the hematopathologists, they provide this expertise on site – both for diagnosis and therapy monitoring in children. Likewise, the vast array of multi-parameter flow cytometry instruments available at the BC Children's Hospital Research Institute (BCCHR) Flow Core Facility supports many of the Reid Lab’s cancer studies, including Dr. Rolf’s translational projects that draw on her expertise as a pediatric oncologist and translational scientist in tumour immunology and ALL-PDX models.
Why is this research important?
In patients, clinical immunophenotyping regularly detects shifts in the expression of molecules on leukemia cells during chemotherapy and relapse. As the disease progresses, changes in this expression could indicate that distinct populations of leukemic cells are developing drug resistance and could potentially relapse. Being able to incorporate the immunophenotypic complexity of leukemic populations could greatly expand the utility of PDX for investigating how ALL progresses and assessing the effectiveness of new therapies.
This study demonstrates that incorporating clinically standardized flow cytometry into PDX studies could greatly expand the investigation of ALL progression biology. Highlighting the importance of their work, the paper was recently featured as one of two must-read articles in the Journal Roundup, a cross-promotion between Cytometry Part A and the European Journal of Immunology.
For further details on this study, read the full article here.
Do you have a study you would like to feature? Please contact core-tech@bcchr.ca and we would love to hear from you.
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