September is Blood Cancer Awareness Month, an important time to raise awareness about the various forms of blood cancer, including leukemia and lymphoma. It also provides an opportunity to educate the public about the cutting-edge research that brings hope for more effective treatment options and improved patient outcomes.
UHN’s Princess Margaret Cancer Centre (PM), one of the world's top cancer research institutions, leads research across various fields. Dr. Robert Kridel, a Clinician Scientist at PM, and his team focus on lymphoma, which is a common cancer affecting around 12,000 Canadians each year.
As a testament to Dr. Kridel’s dedication to understanding this disease, he recently achieved a remarkable feat, publishing three papers as senior author in the span of 24 hours. These studies, built on years of collaboration within UHN and beyond, reflect the significant progress being made in lymphoma research.
“Lymphomas are a type of blood cancer that affect the lymphatic system, a crucial part of the immune system. It happens when lymphocytes—a type of white blood cell—grow uncontrollably, forming tumours,” explains Dr. Kridel. “Lymphomas are a diverse group of diseases, making treatment challenging because each type can be very different. Some are aggressive but treatable, while others are slow growing but incurable.”
Dr. Kridel’s research centres on understanding this diversity of lymphoma. “We study lymphoma’s diversity to predict how patients will respond to treatment,” says Dr. Kridel. “We are also working on new therapies that precisely target lymphoma cells.”
Using genetic analysis to understand and treat lymphomas
In the first of their three studies, Dr. Kridel’s team, including first author and postdoctoral researcher Dr. Michael He, investigated an approach to treat lymphomas in patients with a specific gene mutation. Past research showed that blocking the enzyme HDAC3 can be effective against these lymphomas; however, tumours lacking this mutation show resistance to the treatment. The team found that turning off a gene called GNAS makes resistant lymphoma cells more sensitive to HDAC3 inhibitors, which could lead to better treatments for patients.
The second study, led by Dr. Kridel and first author Victoria Shelton, a computational biologist in his lab, examined why follicular lymphoma varies so much in symptoms and patient outcomes. Using a statistical model to analyze genetic differences in tumour samples from 713 patients, the researchers identified five distinct genetic subtypes, each with unique mutations. These subtypes were linked to specific clinical features, such as disease stage and treatment response, which may help guide treatment decisions.
In their third study, Dr. Kridel’s team, including first author Dr. Samantha Hershenfeld, a hematology fellow, analyzed gene mutations in 117 patients to see if they could predict how well radiotherapy treatment would work for early-stage follicular lymphoma. The findings suggest that gene mutations did not predict patient outcomes and that other biomarkers, such as those derived from the tumour microenvironment, may be better indicators.
“I am incredibly proud of the team,” concludes Dr. Kridel. “They have worked tirelessly to bring these studies to fruition. Science is a team sport, and I want to give credit to everyone in my lab who made this possible.”
Watch the video below to learn more about Dr. Kridel's work in lymphoma research and why it matters.
Dr. Kridel discusses his research on lymphoma.
These studies were supported by the Leukemia & Lymphoma Society of Canada, the Leukemia & Lymphoma Society (US), the Canadian Cancer Society, the Terry Fox Research Institute, the Lymphoma Research Foundation, and The Princess Margaret Cancer Foundation.
Dr. Robert Kridel is an Associate Professor in the Temerty Faculty of Medicine at the University of Toronto.
He MY, Tong KI, Liu T, Whittaker Hawkins R, Shelton V, Zeng Y, Bakhtiari M, Xiao Y, Zheng G, Sakhdari A, Yang L, Xu W, Brooks DG, Laister RC, He HH, Kridel R. GNAS knockout potentiates HDAC3 inhibition through viral mimicry-related interferon responses in lymphoma. Leukemia. 2024 Aug 8. doi: 10.1038/s41375-024-02325-4.
Shelton V, Detroja R, Liu T, Isaev K, Silva A, Passerini V, Bakhtiari M, Calvente L, Hong M, He MY, Modi S, Hershenfeld SA, Ludvigsen M, Madsen C, Hamilton-Dutoit S, d'Amore FA, Brodtkorb M, Johnson NA, Baetz T, LeBrun D, Tobin JWD, Gandhi MK, Mungall AJ, Xu W, Ben-Neriah S, Steidl C, Delabie J, Tremblay-LeMay R, Jegede O, Weigert O, Kahl B, Evens AM, Kridel R. Identification of genetic subtypes in follicular lymphoma. Blood Cancer J. 2024 Aug 7;14(1):128. doi: 10.1038/s41408-024-01111-w.
Hershenfeld SA, Tobin JWD, Shelton V, Calvente L, Lajkosz K, Liu T, Brodtkorb M, d'Amore FA, Ludvigsen M, Baetz T, LeBrun D, Johnson N, Crump M, Hong M, Kuruvilla J, Tremblay-LeMay R, MacManus M, Tsang R, Hodgson DC, Gandhi MK, Kridel R. Single gene mutations and prognosis in limited-stage follicular lymphoma treated with radiation therapy. Br J Haematol. 2024 Aug 7. doi: 10.1111/bjh.19698.