A new study shows that newly acquired cell mutations interact with inherited mutations-those passed down by your parents-in crucial ways that influence your lifetime cancer risk.
As we age, our cells replicate, and the DNA in these cells can acquire mistakes-or mutations-every time the sequence is copied. most newly acquired mutations are harmless, but some can tip the balance toward cancer development later in life.
Understanding the interactions between inherited and acquired mutations could guide development of new methods for early detection and prevention of cancer.
The research in Nature Genetics focused specifically on the risk of blood cancers such as acute myeloid leukemia (AML), although interactions between inherited and acquired mutations likely have roles in other types of cancer.
Inherited mutations are carried in the egg and sperm and are thus present in every cell starting at birth, whereas acquired mutations accumulate gradually with age in different cells. Led by Kelly Bolton, an assistant professor of medicine in the Division of Oncology at Washington University School of Medicine in St. Louis and the study’s senior author, the research team set out to understand how interactions between these two types of mutations influence a person’s risk of developing blood cancer.
In particular, they focused on a blood condition called clonal hematopoiesis that is known to increase a person’s risk of developing blood cancer. Clonal hematopoiesis is caused by a mutation in blood stem cells-cells that give rise to all the different cell types in the blood-that gives those cells a slight survival advantage over the normal stem cells. Such stem cell clones multiply more and are at risk of transforming to blood cancer.
“Most people with clonal hematopoiesis never develop blood cancer,” says Bolton, who treats patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine.
“To some measurable degree, it’s a normal aging process. However, we think that many if not all individuals who develop blood cancer pass through a phase of clonal hematopoiesis at some point.We are still in the early stages of trying to figure out which individuals with clonal hematopoiesis will go on to develop blood cancer and which will not.”
Studying genomic data of more than 730,000 people, including from blood samples, the researchers found that clonal hematopoiesis was more common among those with inherited mutations in certain genes already known to increase the risk of cancer.
They also found that such inherited mutations had an impact on patterns of newly acquired mutations that cause clonal hematopoiesis. If stem cell clones go on to acquire just a handful more harmful mutations, the clonal hematopoiesis can transform into a blood cancer, such as AML, in which the cells stop doing their jobs and multiply until they crowd out healthy cells.
With the goal of finding ways to detect and eliminate pre-cancerous cells in people at high risk of blood c
Genetic Study Pinpoints Mutations for earlier Blood Cancer Detection
A new study from Washington University in St. Louis has identified key genetic mutations that could pave the way for earlier detection of leukemia and other blood cancers. Researchers hope this will lead to preventative treatments before the disease progresses to a more challenging-to-treat stage.
The study, published recently, focuses on clonal hematopoiesis, a condition where mutated blood stem cells accumulate in the body.While these mutations don’t instantly cause cancer, they substantially increase the risk of developing leukemia and other blood disorders later in life. Currently, identifying clonal hematopoiesis requires specialized, and often unavailable, blood tests. Individuals can have these potentially perilous mutations without showing any abnormalities in standard blood tests performed during routine checkups.
“Because leukemia is so hard to treat, we hope to find ways to intervene early-when it’s still pre-cancerous-so we can stop clonal hematopoiesis from transforming into leukemia,” explains Dr. Margaret Bolton, a lead researcher on the project.
The research team analyzed data from the UK Biobank and the All of Us Research Programme, identifying specific genes that appear to be crucial in the development of clonal hematopoiesis.Pinpointing these genes is a critical step towards developing new blood tests capable of detecting these mutations before customary blood tests reveal a problem.
Researchers are already investigating the potential of targeted therapies to halt the expansion of these mutated blood stem cell clones.Clinical trials are underway testing IDH1 and IDH2 inhibitors – drugs designed to target specific mutations – in individuals already identified as having clonal hematopoiesis with abnormal blood cell counts. However, the ultimate goal is to identify individuals at risk before they reach this stage.
“We are hopeful about the prospects of these preventive treatments, but we would like to have tools to identify these individuals even earlier, before their blood cell counts become abnormal,” Bolton says. “There are a lot of targeted therapies that are being developed right now and new approaches researchers are looking at for this purpose.”
This research was supported by grants from the National institutes of Health (NIH), the MDS Foundation, the Children’s Finding Institute, the Prostate Cancer Foundation, the Edward P. Evans Foundation, the SciLifeLab & Wallenberg Data Driven Life Science Program, the Swedish Cancer Foundation, the Swedish Research Council, Burroughs Wellcome Fund, Pew Charitable Trusts, and Hevolution/AFAR.
Sources:
Washington university in St. louis. (2024, August 29). Genetic study suggests ways to catch blood cancer earlier. https://source.washu.edu/2024/08/genetic-study-suggests-ways-to-catch-blood-cancer-earlier/
Futurity. (2024, August 29). New clues to stopping leukemia before it starts. https://www.futurity.org/leukemia-cancer-chemotherapy-2789122-2/