Blood biomarkers tip off pre-malignant cancers

Early detection of blood cancers may be getting a big push with the discovery of a pre-cancerous state of genetic mutation in lymphomas, leukemia, myelodysplastic syndrome and other blood diseases. The biomarker is easily detectable in peripheral blood samples, according to two major studies published online Nov. 26 in the New England Journal of Medicine.

The Harvard and Broad Institute of MIT studies connected certain somatic mutations—meaning those that develop over time through genetic and epigenetic variations in cells—to an increased risk of developing blood cancer. Patients over 70 who were found to have a certain subset of mutations were 10 times more likely to develop blood disease. Age was an important risk factor and significantly increased the likelihood that the mutated subset would appear with each passing decade. In general, though, total risk of developing blood cancer in five years was approximately 5 percent for study subjects with the mutations.

Siddhartha Jaiswal, MD, PhD, a pathologist from Harvard Medical School, and colleagues conducted one of the studies, which identified clonal hematopoiesis from expanding cells that may kick off mutations found in the blood. In previous studies, researchers found that as many as 25 percent of women over the age of 65 have alterations in the pattern of X-chromosome inactivation in the blood, which may be due to mutations in TET2.

For this study, researchers sequenced DNA samples from 22 different cohorts from three consortia. This translated to peripheral-blood cell samples of 17,182 people. A total of 805 somatic variants were identified as candidates for tripping off clonal hematopoiesis. The most common gene to show up as mutated was DNMT3A, with TET2 and ASXL1 coming up behind.

“Perhaps the most surprising finding in our study was the increased mortality among persons with clones as compared with those without clones,” wrote Jaiswal et al. “This effect is much larger than can be explained by hematologic cancers alone, is synergistic with high red-cell distribution width (which could be a marker of perturbation of hematopoiesis due to the clone), and may be related to the increased risk of incident coronary heart disease and ischemic stroke in persons with clones.”

The authors noted that it would be premature to screen for these candidates until researchers have a better understanding of precancerous states and all of the variables that lead up to the development of blood cancers.