Abstract
The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms, in which a stem cell lesion induces an autonomous proliferative advantage. In addition to the JAK2V617 mutation several other mutations have been described. Recently chronic inflammation has been proposed as a trigger and driver of clonal evolution in MPNs. Herein, it is hypothesized that sustained inflammation may elicit the stem cell insult by inducing a state of chronic oxidative stress with elevated levels of reactive oxygen species (ROS) in the bone marrow, thereby creating a high-risk microenvironment for induction of mutations due to the persistent inflammation-induced oxidative damage to DNA in hematopoietic cells. Alterations in the epigenome induced by the chronic inflammatory drive may likely elicit a "epigenetic switch" promoting persistent inflammation. The perspectives of chronic inflammation as the driver of mutagenesis in MPNs are discussed, including early intervention with interferon-alpha2 and potent anti-inflammatory agents (e.g. JAK1-2 inhibitors, histone deacetylase inhibitors, DNA-hypomethylators and statins) to disrupt the self-perpetuating chronic inflammation state and accordingly eliminating a potential trigger of clonal evolution and disease progression with myelofibrotic and leukemic transformation.
| Original language | English |
|---|---|
| Journal | Leukemia Research |
| Volume | 37 |
| Issue number | 2 |
| Pages (from-to) | 214-20 |
| Number of pages | 7 |
| ISSN | 0145-2126 |
| DOIs | |
| Publication status | Published - Feb 2013 |
Keywords
- Animals
- Bone Marrow Neoplasms
- Cell Transformation, Neoplastic
- Chronic Disease
- Disease Progression
- Epigenesis, Genetic
- Gene Expression Regulation, Neoplastic
- Genomic Instability
- Humans
- Inflammation
- Janus Kinase 2
- Mutagenesis
- Mutation
- Neoplasms
- Polycythemia Vera
- Primary Myelofibrosis
- Signal Transduction
- Stem Cell Niche
- Thrombocythemia, Essential
