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<p>Folates serve as key enzyme cofactors in several biological processes. Folic acid supplementation is a cornerstone practice but may have a “dark side”. Indeed, the accumulation of circulating unmetabolized folic acid (UMFA) has been associated with various chronic inflammatory conditions, including cancer. Additionally, by engaging specific folate receptors, folates can directly stimulate cancer cells and modulate the expression of genes coding for pro-inflammatory and pro-fibrotic cytokines.</p><p>This evidence could be extremely relevant for myelofibrosis (MF), a chronic myeloproliferative neoplasm typified by the unique combination of clonal proliferation, chronic inflammation, and progressive bone marrow fibrosis. Folate supplementation is frequently associated with conventional or investigational drugs in the treatment of MF-related anemia to tackle ineffective erythropoiesis. In this review, we cover the different aspects of folate metabolism entailed in the behavior and function of normal and malignant hematopoietic cells and discuss the potential implications on the biology of myelofibrosis.</p>

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Folate metabolism in myelofibrosis: a missing key?

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月23日

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  • Giacomo Maria Cerreto,
  • Giulia Pozzi,
  • Samuele Cortellazzi,
  • Livia Micaela Pasini,
  • Orsola Di Martino,
  • Prisco Mirandola,
  • Cecilia Carubbi,
  • Marco Vitale,
  • Elena Masselli

摘要

Folates serve as key enzyme cofactors in several biological processes. Folic acid supplementation is a cornerstone practice but may have a “dark side”. Indeed, the accumulation of circulating unmetabolized folic acid (UMFA) has been associated with various chronic inflammatory conditions, including cancer. Additionally, by engaging specific folate receptors, folates can directly stimulate cancer cells and modulate the expression of genes coding for pro-inflammatory and pro-fibrotic cytokines.

This evidence could be extremely relevant for myelofibrosis (MF), a chronic myeloproliferative neoplasm typified by the unique combination of clonal proliferation, chronic inflammation, and progressive bone marrow fibrosis. Folate supplementation is frequently associated with conventional or investigational drugs in the treatment of MF-related anemia to tackle ineffective erythropoiesis. In this review, we cover the different aspects of folate metabolism entailed in the behavior and function of normal and malignant hematopoietic cells and discuss the potential implications on the biology of myelofibrosis.