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Scientists decipher the mechanism of rare blood diseases!
Scientists at Mainz University Medical Center are decoding the mechanism of action of HDAC inhibitors in myeloproliferative neoplasms.
Scientists decipher the mechanism of rare blood diseases!
Scientists at Mainz University Medical Center have made significant progress in researching myeloproliferative neoplasms (MPN). These rare blood diseases are characterized by an overproduction of blood cells in the bone marrow. Every year around 4,700 people in Germany, mainly older people, develop MPN, which can progress into acute myeloid leukemia, which is often fatal if left untreated. MPN is characterized by mutations in the hematopoietic system, particularly the Janus kinase 2 (JAK2) mutation, which represents a key risk factor.
The research results were published in the specialist journalSignal Transduction and Targeted Therapypublished and shed light on the mechanism of action of histone deacetylase inhibitors (HDAC inhibitors). These drugs are currently being tested to specifically block the HDAC enzymes and thus kill cancer cells. The molecular mechanism behind HDAC inhibitors in MPN was not fully understood. However, recent research shows that the SIAH2 protein plays a key role in causing damaged target proteins to break down.
Mechanism of HDAC inhibitors
The study reveals that HDAC1 and HDAC2 regulate the activity of SIAH2. Blocking these deacetylases increases acetylation, which improves the stability of SIAH2 and ultimately leads to the selective death of MPN cells. These findings could help develop gentler therapies for MPN patients and ultimately prevent disease progression.
MPN often develop gradually, often over years without any noticeable symptoms. There are different types of MPN, classified depending on the type of blood cell overproduced. The most common types include:
| type.type | Description |
|---|---|
| Polycythemia vera | Overproduction of red blood cells leads to thickened blood and increased risk of thrombosis. |
| Myelofibrosis | Abnormal stem cells create scar tissue in the bone marrow, leading to anemia. |
| Essential thrombocythemia | Overproduction of platelets increases the risk of blood clots. |
| Chronic eosinophilic leukemia (CEL) | Overproduction of eosinophils can progress to acute myeloid leukemia. |
| Chronic myelogenous leukemia (CML) | Overproduction of granulocytes affects other blood cell types. |
| Chronic neutrophilic leukemia (CNL) | Overproduction of neutrophils. |
| Myeloproliferative neoplasm, unclassifiable (MPN-U) | Could involve different blood cell types. |
Conclusions and future therapies
Current research expands the understanding of the pathogenetic mechanisms that contribute to the development of MPN. These diseases probably arise as part of a multi-step process. Some factors, such as mutated genes or individual age, play a role. Many of the MPN patients carry the 'driver' mutation without additional mutations, which influences their choice of therapy.
In summary, the latest research on HDAC inhibitors could not only contribute to a better understanding of MPN, but also offer new therapeutic approaches to sustainably improve the lives of those affected. The research team's collaboration with partners from Hanover and Mainz is an important step in the right direction to meet the challenges of these complex blood diseases.
Mainz University Medical Center reports that focus has been placed on developing effective therapies.
Cleveland Clinic explains the different types and their effects on health.
Oncopedia provides comprehensive guidelines for further research and treatment of MPN.