Scientists have identified a way to promote chemotherapy to combat the most common type of leukemia: acute myeloid leukemia.
In a recent study, the researchers found that acute myeloid leukemia (AML) triggers bone marrow vascular leakage, leading to the inability of chemotherapy drugs to reach leukemia cells, reducing the effectiveness of chemotherapy. However, such leakage can be prevented by the use of drugs for treating cardiovascular diseases, thereby increasing the effectiveness of chemotherapy.
Diana Passaro from the British research institute, the Francis Creek Institute, and colleagues published the findings in CancerCall.
AML is a cancer that begins in the myeloid cells and is a form of white blood cells (except lymphocytes), red blood cells, or platelets that are immature.
Approximately 21.380 new AML cases are expected in the United States this year, and approximately 10,590 patients may die from such diseases. The survival rate of AML patients is very low compared to other types of cancer. According to the National Cancer Institute (NCI), only 26.9% of patients diagnosed with AML survived for more than 5 years.
Chemotherapy is the primary treatment for most AML patients. However, studies have shown that one in five patients do not respond to initial chemotherapy, and about 40% to 60% of patients have experienced relapse after chemotherapy. Resistance to chemotherapeutic drugs is the main culprit for chemotherapy failure.
AML increases nitric oxide production
The research team wants to gain insight into the mechanisms of chemotherapy resistance in AML patients.
In order to achieve the research purpose, the research team extracted the bone marrow of AML patients and injected them into mice. The bone marrow of these mice and healthy mice were then compared by in vivo microscopy. In vivo microscopy is a common tool used to study the cellular and molecular processes of living animals. The researchers found that bone marrow vessels in AML mice leaked compared to healthy mice.
Further studies have also shown that AML mice have significantly lower oxygen levels, the team speculated that is the increase in oxygen uptake by leukemia cells.
This oxygen deficiency leads to an increase in the production of nitric oxide (NO), which helps to relax blood vessels and increase the flow of oxygen-rich blood.
The team speculated that NO loosened the bone marrow blood vessels of AML mice, allowing blood to leak through the dense blood vessel wall, and leukemia cells escaped chemotherapy.
Passaro explained that when the blood vessel wall leaks and the blood flow in the bone marrow is irregular, leukemia cells can easily find the location to hide and evade chemotherapy drugs. Leakage of blood vessels prevents oxygen from reaching part of the bone marrow, exacerbating NO production and leakage.
In order to reinforce their findings, the researchers also compared the bone marrow of AML patients with healthy people through biopsy. They found that the bone marrow of patients with AML showed a higher NO content, and the high NO content was associated with poor chemotherapy response.
No blockers prevent vascular leakage
Next, the researchers used drugs to treat AML mice to prevent NO production.
This is not only to prevent leakage of bone marrow blood vessels and to restore normal blood flow, but also to allow chemotherapy drugs to successfully reach leukemia cells.
In addition, the team found that NO inhibitors can increase the number of bone marrow stem cells in AML mice, which can help the number of healthy cells exceed leukemia cells, thereby promoting the enhancement of chemotherapy.
There is a need for further research to confirm that NO-blockers can help patients with AML improve chemotherapy efficacy, and the researchers are very optimistic.
Another research author, Dominique Bonnet, said: “Our findings suggest that this may indicate that AML patients will respond better to chemotherapy.” (Floating Dream 206589)