1. Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology
- Author
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Anna Rita Migliaccio, Claudio Bardelli, Maria Teresa Bochicchio, Maria Zingariello, Zimran Eran, Eran Z., Zingariello M., Bochicchio M.T., Bardelli C., and FRANCO MIGLIACCIO ANNA RITA
- 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 - 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.
- Published
- 2019