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The mysterious origins of myelofibrosis: Why does the bone marrow become fibrous
Primary Myelofibrosis (PMF) is a rare bone marrow blood cancer and one of the two major types of myeloproliferative neoplasms classified by the World Health Organization. Although the exact origins of the disease remain unclear, its main feature is fibrosis within the bone marrow, which prevents the production of normal blood cells. Treatment options for this condition are limited, and Taiwan's medical community is still working to explore better treatments.
According to the latest medical research, 90% of myelofibrosis patients are associated with mutations in the JAK2, CALR or MPL genes. How do these mutations affect the development of myelofibrosis?
Symptoms and Signs
The main symptoms of myelofibrosis include an enlarged spleen (splenomegaly), with possible abdominal distension, bone pain, and easy bruising. Symptoms may also include:
- Persistent fatigue
- Fever and night sweats
- Weight loss and loss of appetite
- Pale complexion and shortness of breath caused by anemia
- Increased risk of infection, such as pneumonia
Pathogenesis
The underlying cause of myelofibrosis is almost always related to acquired mutations in hematopoietic stem cells or their precursors in the bone marrow. These mutations are not limited to myelofibrosis but can also be detected in other myeloproliferative neoplasms such as polycythemia vera and primary thrombocythemia vera.
Mutations in the JAK2 protein cause a variation called V617F, which makes blood-forming cells more sensitive to growth factors that affect blood production.
As the disease progresses, fibrotic tissue gradually replaces normal hematopoietic tissue, resulting in insufficient production of all blood cell types, a condition known as pancytopenia. In almost all cases of myelofibrosis, the proliferation of megakaryocytes and their abnormal shape are very obvious, which is also one of the important reasons for the formation of fibrosis.
Diagnostic Methods
Myelofibrosis usually develops gradually in adults over 50 years of age. The key to diagnosis is a bone marrow biopsy, which is essential to determine the extent of fibrosis. Based on the grade of fibrosis, physicians can effectively differentiate between overt myelofibrosis and a prefibrotic state.
Treatment Options
Currently, the only treatment considered curative is allogeneic stem cell transplantation, but this approach carries high risks. For most patients, supportive care includes regular folic acid, painkillers and blood transfusions, while drugs like Ruxolitinib are the latest to emerge for the disease, with preliminary research results showing significant reductions in spleen volume and improvement in symptoms. However, the true impact of these drugs on patients' overall survival is still under investigation.
It has been reported that the therapeutic drugs Fedratinib and Momelotinib approved by the US FDA in 2019 and 2023 make up for the treatment needs of current patients, especially those suffering from anemia.
Historical evolution
Myelofibrosis research dates back to 1879, when Gustav Heuck first described the condition. The disease was identified as a myeloproliferative disease by William Dameshek in 1951 and was officially named primary myelofibrosis by the WHO in 2008.
Current research is ongoing, and the desire to gain a more fundamental understanding of myelofibrosis is growing. With the advancement of science and technology, will there be more breakthroughs in the future that explain the causes of the disease and provide more effective treatment options?
