Friday, September 17, 2021

How the impact of chemotherapy on healthy cells affects the development of blood cells

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Patients with cancer (purple) exposed to chemotherapy can damage the DNA of cells (orange stars) and develop treatment-related acute myeloid leukemia (tAML). Non-malignant hematopoietic cells upon exposure to chemotherapy face a population-decreasing bottleneck, leading to the development of AML over time. Credit: Institute for Research in Biomedicine (IRB Barcelona)

Some types of chemotherapy eliminate cancer cells by damaging the DNA. These drugs can also affect healthy cells, and damage can cause mutations that persist after treatment.

Researchers at the Institute for Biomedical Genomics in IRB Barcelona, ​​led by ICREA researcher Dr. Núria Lopez Bigas, have identified “footprints” (in the form of DNA). mutation) Left by platinum-based chemotherapy in the case of acute myeloid leukemia (AML) associated with previous chemotherapy treatment of solid tumors.

“In this study, we especially chemical treatment of Healthy cellsTo understand whether the onset of AML is before or after the patient’s exposure to chemotherapy, “said Dr. Abergonzales Perez, a researcher who co-led the project with Dr. Lopez Bigas.Platinum-based chemotherapy, detection of this mutant fingerprint in all AML cell It can be confirmed that the development of treatment-related AML follows exposure to these drugs, “he explains.

Specifically, the researchers were able to identify the “footprints” of platinum-based chemotherapy (cisplatin, oxaliplatin, and carboplatin) in the blood cells of patients with secondary AML. In contrast, treatments based on 5-fluorouracil or capecitabine, despite being associated with cases of secondary AML, leave a detectable footprint in healthy blood cells, probably due to a different mechanism of action. I didn’t understand.

Clonal hematopoies and secondary AML

Clonal hematopoies are a common process in the elderly, where hematopoietic cells regenerate more efficiently than other cells and make up a significant portion of blood cells over time. Clonal hematopoies also occur as a result of exposure to some chemotherapy. When this process begins after exposure to treatment, mutations in platinum-based chemotherapy are detected, as in AML. However, the authors have not identified these mutations. This means that the onset of clonal hematopoies precedes treatment with chemotherapy, which favors its development.

“Our study can identify whether clonal hematopoies have already begun before chemotherapy and establish a temporal relationship,” said the lead author of the study and a graduate of IRB Barcelona. , Says Dr. Oriol Pitch, now a postdoctoral fellow at Francis. Click Institute in London.

Map of genetic changes caused by chemotherapy

In 2019, the Biomedical Genomics Laboratory published a paper identifying the “footprints” left on healthy cells by six commonly used treatments for cancer. In this regard, they observed that some of these chemotherapies change DNA 100 to 1000 times faster than the processes associated with aging.

Genetic changes caused by identified cancer treatments

For more information:
Oriol Pich et al, Evolution of Hematopoietic Cells under Cancer Treatment, Nature Communications (2021). DOI: 10.1038 / s41467-021-24858-3

Quote: How the effects of chemotherapy on healthy cells affect blood cell development (September 14, 2021) September 14, 2021 Obtained from -chemotherapy-healthy-cells-affects. html

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