People with shortened telomeres caused by rare disorders may be more likely to have blood cancers such as leukaemia or myelodyplastic syndrome (MS). Now researchers have discovered several “self-correcting” genetic mutations in bone marrow that may protect such patients from these cancers.
In a study published in the Journal of Clinical Investigation, these mutations can serve as biomarkers to indicate if patients with short telomere syndromes (STS) are likely to develop blood cancers.
“These are the most common cancers we see in patients with short telomere syndromes,” said Mary Armanios, MD, director of the Telomere Center and professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “We know that at a certain point, the cells of patients with shortened telomeres either become cancerous or stay healthy.”
Dr Armanios and her team suspected that a self-correcting mechanism in areas of the body with high cell turnover, such as bone marrow, was allowing normal cells to turn malignant. Instead, it appears this mechanism protects against cells from becoming cancerous.
As over 300 billion blood cells are produced in the bone marrow daily, the researchers suspected they could find evidence of cellular self-correction in this area of the body, especially amid the spongey interior of bones, where quick adaptation is crucial for high-volume cell production.
The researchers tested the bone marrow and blood cells of 84 study participants divided into three groups: Those with STS and MS or leukaemia; those with short telomere syndromes and no MS or leukemia; and those in the control group without short telomere syndromes or any cancers.
Using ultra-deep genetic sequencing which picks up hard-to-detect mutations, Armanios and her team observed genetic mutations and self-correction in several telomere-associated genes. Nearly a quarter of patients with STS had these mutations, some even showing multiple mutations.
One such mutation in a gene called TERT enables the production of crucial parts of telomerase, which stabilises telomeres. By boosting telomerase production and overwriting faulty copies of the TERT gene, the researchers found that bone marrow cells seemed to self-correct to avoid becoming cancerous.
“Our findings speak to the versatility of the bone marrow and other areas with high cell turnover in the body,” says Armanios. “Such advantageous mutations provide the body with a better chance to protect itself. These findings may be important in the screening process of shortened telomere patients so that we can predict who may be protected from cancer.”
Source: John Hopkins Medicine
