Researchers at the Princess Margaret Cancer Centre (PM) have identified a new classification of T-cell acute lymphoblastic leukemia (T-ALL), an aggressive form of bone marrow and blood cancer. This classification offers new hope for personalized therapy.
In T-ALL, white blood cells called T-cells, which are important for fighting off infections, fail to develop properly. These abnormal blood cells then crowd out normal blood cells. Despite treatment advances improving survival rates, many patients do not respond to the standard first-line treatment—induction chemotherapy—and subsequently relapse, leading to poor outcomes.
“There is a need to better stratify patients and personalize treatments,” says Dr. Anastasia Tikhonova, a Scientist at PM and co-senior author of the study. “Currently, immunophenotyping—a method that classifies patients by analyzing the surface proteins of cancer cells—helps identify subgroups. However, even within the same immunophenotype, patients respond differently to treatment, suggesting more diverse leukemic cases.”
The team, also led by Dr. Mark Gower, first author of the study and Dr. Soheil Jahangiri, co-senior author, analyzed the molecular and genetic profiles of patient bone marrow samples at the single-cell level to find new biomarkers of high-risk disease.
They found about one-third of these samples showed elevated markers of inflammation and had a more immature, stem cell-like state compared to other T-ALL samples—a hallmark of cancer initiation and progression.
The team developed an inflammatory gene score to identify patients with this inflammatory T-ALL subtype. They discovered that these patients had poor treatment responses and lower event-free survival—the period a patient remains free of disease progression or other complications.
Interestingly, although inflammatory T-ALL cells were resistant to the standard induction therapy agent dexamethasone, they were sensitive to venetoclax, a therapy used for other blood cancers. These findings suggest that identifying patients with inflammatory leukemia could lead to treatment strategies, such as venetoclax, pending further investigation.
The paper was selected for the cover of the journal Science Translational Medicine.
Mark Gower, a Postdoctoral Researcher at PM is first author of the study.
Dr. Anastasia N. Tikhonova, a Scientist at PM and Assistant Professor in the Department of Medical Biophysics at the University of Toronto (U of T) is a co-senior author of the study.
Dr. Soheil Jahangiri is an Adjunct Scientist at PM and a co-senior author of the study.
This work was supported by the Canadian Institutes for Health Research, the American Society of Hematology, the V Foundation, the J.P. Bickell Foundation, the Ontario Institute for Cancer Research, Gilead Sciences, and The Princess Margaret Cancer Foundation.
For a list of competing interests by a few of the co-authors, see the manuscript.
Gower M, Li X, Aguilar-Navarro AG, Lin B, Fernandez M, Edun G, Nader M, Rondeau V, Arruda A, Tierens A, Eames Seffernick A, Pölönen P, Durocher J, Wagenblast E, Yang L, Lee HS, Mullighan CG, Teachey D, Rashkovan M, Tremblay CS, Herranz D, Itkin T, Loghavi S, Dick JE, Schwartz G, Perusini MA, Sibai H, Hitzler J, Gruber TA, Minden M, Jones CL, Dolgalev I, Jahangiri S, Tikhonova AN. An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup. Sci Transl Med. 2025 Jan;17(779):eadr2012. doi: 10.1126/scitranslmed.adr2012. Epub 2025 Jan 1.