Preclinical research indicates that the fat mass- and obesity-associated protein FTO (an N6-methyladenosine [m6A]) is involved in the development of acute myeloid leukemia (AML) and may affect response to treatment. FTO regulates the expression of a set of genes through a mechanism involving RNA modification, which increases the proliferation of leukemia cells and inhibits response to treatment, according to Jianjun Chen, PhD, of the University of Cincinnati in Ohio, and authors who published their findings in Cancer Cell.
“Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia,” said Dr. Chen. “In addition, given the functional importance of FTO in the formation of leukemia and drug response, targeting FTO signaling may present a new therapeutic strategy to treat leukemia.”
The researchers compared two microarray datasets from AML and control samples, finding that FTO was highly expressed in AML samples with t(11q23)/MLL rearrangements, t(15;17)/PML-RARA, FLT3-ITD, and/or NPM1 mutations. In addition, they found that genes such as ASB2 and RARA, which reportedly inhibit leukemia cell growth and impact treatment response, were suppressed in the AML samples with higher FTO expression; this was attributed to FTO-controlled decreased stability of their mRNA and connected to FTO’s m6A demethylase activity.
Previous studies have linked obesity to multiple myeloma, as well.
Source: Li Z, Weng H, Su R, et al. FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase. Cancer Cell. 2016 December 13. [Epub ahead of print]