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Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology
- Source :
- F1000Research
- Publication Year :
- 2019
- Publisher :
- F1000 Research Ltd, 2019.
-
Abstract
- Myelofibrosis is the advanced stage of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by systemic inflammation, hematopoietic failure in the bone marrow, and development of extramedullary hematopoiesis, mainly in the spleen. The only potentially curative therapy for this disease is hematopoietic stem cell transplantation, an option that may be offered only to those patients with a compatible donor and with an age and functional status that may face its toxicity. By contrast, with the Philadelphia-positive MPNs that can be dramatically modified by inhibitors of the novel BCR-ABL fusion-protein generated by its genetic lesion, the identification of the molecular lesions that lead to the development of myelofibrosis has not yet translated into a treatment that can modify the natural history of the disease. Therefore, the cure of myelofibrosis remains an unmet clinical need. However, the excitement raised by the discovery of the genetic lesions has inspired additional studies aimed at elucidating the mechanisms driving these neoplasms towards their final stage. These studies have generated the feeling that the cure of myelofibrosis will require targeting both the malignant stem cell clone and its supportive microenvironment. We will summarize here some of the biochemical alterations recently identified in MPNs and the novel therapeutic approaches currently under investigation inspired by these discoveries.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Fusion Proteins, bcr-abl
Myelofibrosis
Review
Disease
Hematopoietic stem cell transplantation
Bioinformatics
Primary Myelofibrosi
0302 clinical medicine
Bone Marrow
Tumor Microenvironment
Medicine
pre-clinical studies
General Pharmacology, Toxicology and Pharmaceutics
Transforming growth factor beta inhibitor
Hematopoietic Stem Cell Transplantation
Myelofibrosi
Articles
General Medicine
animal models
3. Good health
Extramedullary hematopoiesis
medicine.anatomical_structure
MDM2 inhibitor
Hematopoiesis, Extramedullary
030220 oncology & carcinogenesis
Stem cell
Pre-clinical studie
Human
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Myeloproliferative Disorders
Humans
Animal model
transforming growth factor beta inhibitors
Combination therapy
Myeloproliferative Disorder
P53
Tumor microenvironment
General Immunology and Microbiology
business.industry
medicine.disease
030104 developmental biology
Primary Myelofibrosis
MDM2 inhibitors
Transforming growth factor beta
Bone marrow
business
Subjects
Details
- ISSN :
- 20461402
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- F1000Research
- Accession number :
- edsair.doi.dedup.....fe3bb328c7f19c47ae82844f8686a796