A protein associated with obesity plays a significant role in the development of leukemia as well as in drug response, researchers have found.
A new study has revealed that FTO — the protein associated with fat mass and obesity — plays a critical cancer-promoting role by regulating expression of a set of genes through a mechanism involving ribonucleic acid (RNA) modification and thereby increasing the reproduction of leukemia cells and prohibiting drug response.
In 2011, Jianjun Chen, Associate Professor at the University of Chicago, US, made the first observation that FTO erases m6A methylation — the most impactful modificator in the RNAs.
In the study, Chen showed that the m6A modification can be reversed.
For the study, the team analysed a microarray dataset of 100 human acute myeloid leukemia (AML) samples from patients and nine normal control samples as well as other large-scale microarray datasets of AML samples.
They found that FTO was highly expressed in various subtypes of leukemia samples such as those that contained chromosome crossover — genetic exchange between chromosomes — or mutations in certain genes.
The high level of FTO expression contributed to cancer cells multiplying and surviving and also promoted the development of leukemia in animal models and the non-response of cancer cells to therapeutic agents.
Additionally, researchers found that genes like ASB2 and RARA, which were reported to inhibit leukemia cell growth and/or mediate the response of leukemia cells to therapeutic agents, were suppressed in the AML samples with higher FTO expression.
The suppression of these genes was attributed to FTO-controlled decreased stability of their mRNA and was connected to FTO’s m6A demethylase activity.
“Our study shows, for the first time, the functional importance of the m6A modification machinery in leukemia,” Chen said, adding that this could help find new therapeutic strategy for leukemia treatment.
The study was published online in the journal Cancer Cell.