by Alan Cocchetto, NCF Medical Director © 2013
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From Fall 2013 Forum

Scientists at the National Institutes of Health continue to make headway in their understanding of several key mechanisms behind cancer-related fatigue. In their latest study, radiation treatments for cancer produced fatigue in patients that was found to correlate with the production of interferon alpha-inducible protein 27, also known as IFI27.

This work supports the notion that external beam radiation therapy causes a fatigue intensification that is a bystander response to radiation. This effect is due to the upregulation of IFI27 which influences both mitochondrial function as well as immune response, both mechanisms tied to cancer-related fatigue.

Since IFI27 induces interferon-alpha, it is intriguing to note that chronic interferon-alpha treatment is associated with an upregulation of a gene called OAS2. This was found to correlate with symptoms associated with fatigue and depression. OAS2 has been found to be upregulated in CFIDS patients.

In our searches on Pubmed, we were able to find that IFI27 is highly upregulated in primary myelofibrosis. Myelofibrosis is a chronic bone marrow disorder in which excessive scar tissue forms in the bone marrow and impairs its ability to produce normal blood cells. Myelofibrosis is thought to be caused by abnormal blood stem cells in the bone marrow. The abnormal stem cells produce more mature cells that grow quickly and take over the bone marrow, causing both fibrosis (scar tissue formation) and chronic inflammation. As a result, the bone marrow becomes less able to create normal blood cells and blood cell production may move to the spleen thereby causing enlargement. Classified as a myeloproliferative neoplasm, myelofibrosis can arise on its own (primary myelofibrosis) or as a progression of polycythemia vera or essential thrombocythemia.

It is particularly interesting to note that myelodysplasia, myelofibrosis and myeloid leukemias run in the same circles sharing similar disease mechanisms. The NCF is aware of a number of PWC's that have been formally diagnosed with either myelodysplasia, polycythemia vera or myeloid leukemias.