Researchers have discovered that severe inflammation may weaken the body’s ability to kill cancerous blood cells in patients with acute myeloid leukemia (AML), according to a new study published by Lasry et al in Nature Cancer. With bone marrow samples from 20 adults and 22 children with AML, the researchers were able to score each patient’s level of inflammation using a new inflammation-associated gene score (iScore) system.
Experiments in human cells also revealed how increasing levels of inflammation—marked by an aggressive reaction of immune cells in the bone marrow—potentially altered the makeup of the B cells and T cells needed to fight AML.
Study Methods and Results
For the investigation, researchers compared bone marrow samples from patients with AML to bone marrow samples from 10 individuals who did not have cancer but were of a similar age, race, and gender.
Some 246 genes tied to inflammation were found to be highly active or less active in adults with the disease, while 187 genes linked to inflammation similarly stood out among children. By factoring in patient survival, researchers narrowed their analysis to 38 relevant genes in adults and 11 in children—and were then able to calculate a score that tied inflammation levels to survivability.
The researchers correlated the iScores to survival rates—with those having the lowest iScores typically surviving the longest. Patients with leukemia who had high iScores died at least 4 years earlier than those with low levels of inflammation.
The researchers indicated that by examining whether patients’ iScores were above or below average, the information gathered by the scores may be used to guide treatment. They proposed that the new iScore system can be added to existing tools for measuring AML severity and used by physicians and patients when deciding between treatment options such as immunotherapy, chemotherapy, or bone marrow transplantation.
“Our scoring system provides an easy tool for physicians and patients to measure their risk from inflammation tied to their leukemia and to adjust their treatment plans accordingly to manage this risk,” explained lead study co-investigator Audrey Lasry, PhD, a postdoctoral fellow in the Department of Pathology at the New York University (NYU) Grossman School of Medicine and Laura & Isaac Perlmutter Cancer Center.
Dr. Lasry and her colleagues noted that some patients, in consultation with their medical providers, may favor immunotherapy to boost their immune cells if their inflammation score is high. Others may choose alternative therapies in cases of low inflammation, because their immune system does not necessarily need reinforcement.
The study further demonstrated that levels of atypical B cells in the bone marrow were also linked to inflammation in both adults and children with AML.
A dozen gene mutations were found to be tied to high iScores and patients with severe cases of AML.
Another key finding was that the effectiveness of some T cells was suppressed in cases of pediatric leukemia with high inflammation but not in adult cases with high inflammation.
Conclusions
“Our study provides the first detailed description of how inflammation alters the tumor microenvironment in both adults and children [with AML],” emphasized lead study co-investigator Bettina Nadorp, PhD, a postdoctoral fellow in the Department of Pathology at the NYU Grossman School of Medicine and Laura & Isaac Perlmutter Cancer Center.
“These study findings suggest that monitoring inflammation in patients with AML and possibly lowering inflammation levels with drug therapy should be considered as part of treatment for the disease,” concluded senior study investigator Iannis Aifantis, PhD, the Hermann M. Biggs Professor and Chair of the Department of Pathology at the NYU Grossman School of Medicine and Laura & Isaac Perlmutter Cancer Center.
In future studies, the researchers plan to analyze bone marrow samples from patients with myelodysplastic syndrome to see if the same risk stratification applies based on inflammation.
The researchers stated that the measurements needed to calculate a patient’s iScore have been made freely available to academic researchers and clinicians in the study manuscript. The research team has a patent application pending for the iScore for any commercial activity resulting from its use. The terms and conditions of this patent are being managed in accordance with the policies of NYU Langone Health.
Disclosure: The research in this study was supported by grants from the National Institutes of Health. Additional funding support was provided by the Vogelstein Foundation, the Evans MDS Foundation, the American Lebanese Syrian Associated Charities, and the Aplastic Anemia and MDS International Foundation. For full disclosures of the study authors, visit nature.com.
