- Fat Mass and Obesity-associated (FTO) protein could be associated with leukemia progression.
- FTO is well known for its association with obesity
- This study provides new targets for drug therapy
A protein that has long
been associated with obesity is now found to increase the risk for leukemia,
according to a study by scientists from The University of Cincinnati. This
could provide new targets for therapy and increase target specific care for
patients with leukemia
The study was led by Dr.
Jianjun Chen who is an associate professor at the Department of Cancer Biology
and identified that the obesity protein, called FTO, changed RNA
modification to promote cancer progression.
‘Fat Mass and Obesity-associated (FTO) protein promoting obesity could promote leukemia.’
(m6A) RNA Methylation
RNA methylation is an important modifier of which genes are transcribed into
RNA. The co-author of the study, Dr. Chuan He, professor of chemistry
at the University of Chicago, discovered that the FTO erases the N6
. In depth sequencing techniques were utilized to identify the
profile of N6 modification across the genome. It was found that nearly one
third of mRNAs from mammalian cells were dependent on N6 methylation.
Previous studies have
identified that N6 methylation of mRNAs and non-coding RNAs are important for
tissue development, renewal of stem cells as well as in differentiation
the importance of this form of methylation in cancer cell progress has not been
identified thus far.
in Acute Myeloid Leukemia
The study involved the
analysis of 100 acute myeloid leukemia
microarray data sets as well
as the data of 9 normal patients. They found that
- FTO was highly expressed in acute myeloid leukemia
- Especially in patients with a mutation at a particular
- The increased level of FTO contributed to the cancer
cells growing and multiplying
- It promoted cancer growth in animal models
- It resulted in non-response to drug treatment
- High level of FTO also corresponded to suppression of
genes like ASB2 (Ankyrin Repeat And SOCS Box Containing 2) and RARA (retinoic acid receptor alpha) that were involved in tumor suppression.
researchers involved in the study believe that the current understanding could
open better treatment methodologies for leukemia. The increase in FTO levels is
not only found in leukemia but is also found in certain other solid tumors.
FTO is called the Fat
mass and obesity protein as it is involved in increasing the risk for obesity
. The FTO protein secreted depends on the
variant of the FTO gene that is inherited. Single nucleotide polymorphisms in
the FTO gene are associated with an increased secretion of the ghrelin hormone,
which is also called the hunger hormone. In people with the normal variant of
the gene, the hormone levels lower after a meal, resulting in feeling of
In the mutant variant of
the gene, the hunger hormone levels remain high even after a meal. This leads
to increased appetite and over eating by the individual, which can lead to
weight gain. People with this variant of the gene need to perform exercises
that were found to control the level of the hunger hormone.
The current study that examined the relevance of
the FTO protein in cancer pathogenesis can be used to design therapeutic
strategies which could control the spread of cancer. Drug targets could be
aimed at lowering levels of this hormone or targeting downstream elements which
could prove to be more effective in cancer treatment than generalized cancer