A proof-of-concept study published in Nature found that there may be identifiable mutations in healthy individuals who are at high risk of developing acute myeloid leukemia (AML), and people may carry this mutation in the blood for years before disease detection.
The researchers used data from the European Prospective Investigation into Cancer and Nutrition study, which started enrolling patients in 1992 from 10 European countries and followed the 521,000 patients for almost 15 years.
— Nature Genetics (@NatureGenet) July 12, 2018
The researchers used deep sequencing to analyze genes that are recurrently mutated in AML to distinguish between those at high risk of developing AML versus those with benign age-related clonal hematopoiesis (ARCH).
— Dr. Thomas Wilckens (@Thomas_Wilckens) July 10, 2018
They assessed peripheral blood cells from 95 individuals that were obtained, on average, 6.3 years before AML diagnosis (pre-AML group) and compared the findings with 414 unselected age- and gender-matched individuals (control group). They found that pre-AML cases were distinct from controls and had more mutations per sample and higher variant allele frequencies.
ARCH (based on putative driver mutations) was found in 73.4% of the pre-AML cases at a median of 7.6 years prior to diagnosis compared with 36.7% of controls. The researchers said they were surprised by this long lead time, as the disease often appears suddenly.
The model was validated in an independent cohort of 29 pre-AML cases and 262 controls.