Abstract
Fanconi anemia (FA) is a rare disorder with the clinical characteristics of (i) specific malformations at birth, (ii) progressive bone marrow failure already during early childhood and (iii) dramatically increased risk of developing cancer in early age, such as acute myeloid leukemia and squamous cell carcinoma. Patients with FA show DNA fragility due to a defect in the DNA repair machinery based on predominately recessive mutations in 23 genes. Interestingly, patients originating from the same family and sharing an identical mutation, frequently show significant differences in their clinical presentation. This implies that epigenetics plays an important role in the manifestation of the disease. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 controls cellular growth, differentiation and apoptosis via the modulation of the immune system. The nuclear hormone activates the transcription factor vitamin D receptor that affects, via fine-tuning of the epigenome, the transcription of >1000 human genes. In this review, we discuss that changes in the epigenome, in particular in immune cells, may be central for the clinical manifestation of FA. These epigenetic changes can be modulated by vitamin D suggesting that the individual FA patient’s vitamin D status and responsiveness are of critical importance for disease progression.
Highlights
Fanconi anemia (FA) is a rare (1:300,000) inherited disease that is one of the leading causes of bone marrow failure and inherited bone marrow failure syndromes [1,2]
FA results from defects in the FA/breast cancer gene DNA repair pathway leading to chromosomal fragility [3]
These epigenetic changes can be modulated by vitamin D suggesting that the individual’s vitamin D status and the personal vitamin D response index of FA patients is of critical importance for the progression of the disease
Summary
Fanconi anemia (FA) is a rare (1:300,000) inherited disease that is one of the leading causes of bone marrow failure and inherited bone marrow failure syndromes [1,2]. A number of these target genes are involved in the modulation of the cells of the immune system, in particular of innate immunity [31], including their growth, differentiation and apoptosis [32] This suggests that vitamin D and its receptor induce epigenetic programing of myeloid cells during immune challenges, such as infections, tissue damage and by pre-neoplastic cells. We discuss the changes in the epigenome, in particular of immune cells, which are of importance for the clinical manifestation of FA These epigenetic changes can be modulated by vitamin D suggesting that the individual’s vitamin D status and the personal vitamin D response index of FA patients is of critical importance for the progression of the disease.
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