Breast Cancer :: Radiotherapy might contribute to leukemia risk in breast cancer patients

Radiation therapy affects not only the cancer mass, but also the surrounding tissues, including the bone marrow. Signals from the cells in the bone marrow damaged by cancer radiotherapy could be involved in the development of secondary acute myeloma by drawing hematopoietic stem cells, the blood-producing cells of the bone marrow, from distant sites into the irradiated bone marrow, according to researchers from the Ontario Cancer Institute. Their findings suggest that local radiotherapy leads to leukemia, even though radiotherapy directly affects only a small fraction of the bone marrow.

While often effective in treating breast cancer, localized radiation therapy increases the risk of developing secondary cancer, which most frequently manifests in the form of acute myeloid leukemia. In breast cancer, less than 10 percent of bone marrow is exposed to radiation therapy, yet a much higher percentage of hematopoietic stem cells could be affected.

To understand this effect, the researchers labeled and tracked the movement of hematopoietic stem cells in an animal model. Following local radiation therapy, they found that more than four times more hematopoietic stem cells accumulated in the irradiated bone marrow, compared to the non-irradiated bone marrow. Through molecular screening, they found that cells in the area were creating an overabundance of three protein signals known to recruit hematopoietic stem cells: SDF1, MMP2 and MMP9.

“Cells within the bone marrow send out these chemical signals as a sort of call for help, which recruits a large number of hematopoietic stem cells into the affected areas, supposedly to replace damaged cells,” said Carlo Bastianutto, Ph.D., a scientific associate at the Ontario Cancer Institute. “In effect, this becomes a trap for this specific population of stem cells, drawing them into the bone marrow present in the radiation field and getting them exposed to the following radiation cycles. This story might repeat at every cycle of radiation therapy, therefore increasing the chance of producing a leukemic stem cell.”

According to the OCI researchers, the recruiting signal might be stopped by chemical blockers, which was shown to inhibit the signals experimentally. “Conceivably, it could be possible to inhibit these chemical signals, and this could reduce the risk of secondary acute myeloid leukemia, but much more research needs to be done,” Bastianutto said.

The researchers believe this model could help prevent acute myeloid leukemia in patients with malignancies other than breast cancer.


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