Factors Associated With AML
Published: 2018-07-09 |
Author: Randi Hernandez |
Source: Cancer Therapy Advisor
Using deep sequencing techniques, investigators of a study published in Nature determined they were able to tease out the predictors that are associated with the development of acute myeloid leukemia (AML).
By looking at the genes that are commonly mutated in AML, and analyzing pre-leukemic hematopoietic stem and progenitor cells (HSPC's), the researchers could provide proof-of-concept for the genetic predictors of the transformation of pre-AML cells into malignant cells, and they could differentiate these aberrations from those that accumulated as a result of age-related clonal hematopoiesis (ARCH).
The investigators compared blood cells from 95 individuals collected 6.3 years prior to an AML diagnosis with 414 people in a control group that were considered healthy individuals. Through a comparison of gene panels, they found driver mutations in 73.4% of the pre-AML cases at a median of 7.6 years before a positive AML diagnosis occurred.
The median number of mutations per participant was significantly higher in the pre-AML group compared with the control group, and in that pre-AML group, 39% of the participants older than 50 years had a driver mutation with a variant frequency of more than 10% compared with 4% in controls.
The most commonly mutated genes access pre-AML cases and controls who had ARCH-RD mutations were DNMT3A and TET2, though these genes are thought to confer less of a risk of malignant transformation. Mutations to TP53 and U2AF1, however, were found to confer a high risk of subsequent AML.
Most importantly, the researchers determined that the "mutational landscape" of ARCH and pre-AML is very different.