Chemotherapy-induced nerve injury in the bone marrow is a crucial lesion that impairs the regeneration of hematopoietic stem cells, leading to anemia, researchers have discovered. Although chemotherapy is already known to cause anemia by damaging the bone marrow, the mechanics behind this process had been unclear.
Paul S. Frenette, MD, director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Albert Einstein College of Medicine (Bronx, New York), and colleagues have now demonstrated that neurotoxic chemotherapies damage sympathetic nerves in the bone marrow itself, impairing the ability of hematopoietic cells to regenerate and to manufacture red blood cells. Earlier research by Frenette had established that sympathetic nerves within bone marrow direct the movement of hematopoietic stem cells.
As they explained in Nature Medicine, the investigators administered seven cycles of cisplatin to mice. This common chemotherapy drug with known neurotoxic effects caused peripheral neuropathy in the mice, similar to that seen in cancer patients. When the mice were then given bone-marrow transplants, those that had undergone cisplatin therapy exhibited delayed recovery of blood counts compared with controls. Mice that had received the non-neurotoxic chemotherapy agent carboplatin, rather than cisplatin, were able to produce blood cells following bone-marrow transplantation.
Frenette’s team also found that using nerve-protecting agents with chemotherapy could reduce injury to sympathetic nerves in the bone marrow. Mice given a reportedly nerve-protecting experimental agent known as 4-methylcatechol along with seven cycles of cisplatin had better response to bone-marrow transplantation than did control mice.