Fat Mass and Obesity-associated (FTO) Protein Linked to Leukemia Risk

Highlights

• 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.

N6-methyladenosine (m6A) RNA Methylation

N6-methyladenosine (m6A) 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 methylation. 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. However, the importance of this form of methylation in cancer cell progress has not been identified thus far.

FTO 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 patients
• Especially in patients with a mutation at a particular region
• 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.

The 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.

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FTO and Obesity

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 fullness.

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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 treatments.

Source-Medindia