A new study from UHN’s Princess Margaret Cancer Centre shows that chemotherapy may cause long-term damage to the body’s bone and blood-forming systems by triggering chronic inflammation in the bone marrow, offering clues to why many cancer survivors face lasting health complications.

Chemotherapy has been a key part of cancer treatment since the 1960s, helping many people with cancer live longer. However, in addition to targeting cancer cells, these drugs can also harm healthy cells in the body. As a result, many cancer survivors face long-term health issues, including weakened bones and problems with blood cell production.

These complications can limit the quality of life, but the mechanisms underlying how chemotherapy drugs disrupt these biological processes are still not fully understood.

Blood cells are produced by a small population of stem cells that reside in specialized areas of the bone marrow called niches. Bone marrow is the soft tissue inside our bones that continuously generates new blood cells and contains many different cell types that work together to keep the blood system healthy. Although the bone marrow can recover from short-term stress, scientists still do not fully understand how chemotherapy affects stem cells and their niches, or how these changes may impair healthy blood production over the long term.

Researchers led by Dr. Anastasia Tikhonova, Senior Scientist at PM, used preclinical models of leukemia treatment to examine the bone marrow niche following treatment with chemotherapy drugs.

“To improve survivorship, we need to better understand how chemotherapy affects not only cancer cells, but also the bone marrow systems that maintain lifelong blood production,” says Dr. Tikhonova.

They found that a widely used chemotherapy drug, doxorubicin, disrupted the structure and function of the bone marrow. The bone marrow niche became less able to support healthy blood stem cell function, resulting in reduced small blood vessels and weakened bone structure.

The study identified a key driver behind these effects: an overactive immune response. After chemotherapy with doxorubicin, immune cells produced high levels of a signaling molecule called interferon-gamma (IFNγ), which increased inflammation and contributed to tissue damage. When researchers blocked IFNγ activity, some of the damage to blood vessels and bone-related cells was partially alleviated.

Further improvements were seen when IFNγ inhibition was combined with a drug that supports blood vessel repair. In addition, bone marrow samples from leukemia patients showed similar patterns after chemotherapy, including increased inflammatory signals and changes in support cells.

Together, the findings highlight IFNγ-driven inflammation as a key mechanism contributing to long-term bone marrow niche damage following doxorubicin-based chemotherapy and point to new potential treatment approaches to preserve bone marrow health in cancer survivors. The researchers hope these findings will guide the development of therapies that reduce long-term side effects of cancer treatment.

Ximing Li is a Doctoral student at UHN’s Princess Margaret Cancer Centre. She is the first author of the study.

Dr. Anastasia Tikhonova is a Senior Scientist at UHN’s Princess Margaret Cancer Centre and Assistant Professor in the Department of Medical Biophysics at the University of Toronto. She is the corresponding author of the study.

This work was supported by the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, the Stem Cell Network, the Natural Sciences and Engineering Research Council of Canada, and The Princess Margaret Cancer Foundation.

Dr. Tikhonova is a Tier 2 Canada Research Chair in Stem Cell Niche Biology.

Li X, Aguilar-Navarro AG, Nader M, Jahangiri S, Lee HS, Edun G, Gower M, Yang D, Fernandez M, Lin B, Oh D, Farhat S, Phillips DM, Bartman S, Murray D, Kaszuba C, Kossinna P, Kamath M, Whyne C, Schwartz G, Bajaj J, Kislinger T, Zhou BO, Coutu D, Akens M, Changoor A, Mallevaey T, Gaiti F, Jones C, Naik S, Minden M, Arruda A, Hitzler J, Lee KJ, Kim YM, Adams RH, Sivara KK, Tikhonova AN. IFN-γ drives long-term bone marrow niche dysfunction following doxorubicin-based chemotherapy. Blood. 2026 Sep 3;148(10):1277-1291. doi: 10.1182/blood.2025030946.