Myelofibrosis pathophysiology
|
Myelofibrosis Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Myelofibrosis pathophysiology On the Web |
|
American Roentgen Ray Society Images of Myelofibrosis pathophysiology |
|
Risk calculators and risk factors for Myelofibrosis pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]
Overview
Genes involved in the pathogenesis of myelofibrosis include JAK2, CALR, and MPL.[1]
Pathogenesis
- Bone marrow is replaced with collagen fibrosis due to cytokines, which are released from abnormal hematopoietic cells.
- Bone marrow is not able to make enough blood cells.
- Anemia, bleeding tendency, and infections may occur.
- Extramedullary hematopoiesis takes place, which causes hepatomegaly and splenomegaly.
- Secondary myelofibrosis may be caused by other blood malignancies, such as leukemia and lymphoma.
Genetics
- Development of myelofibrosis is the result of multiple genetic mutations.[2]
- Genes involved in the pathogenesis of myelofibrosis include:[1][3][4]
- Approximately 90% of those with myelofibrosis have one of these mutations. These mutations are not specific to myelofibrosis, and are linked to other myeloproliferative disorders, specifically essential thrombocythemia.[2]
- The V617F mutation to the JAK2 protein is found in approximately half of individuals with primary myelofibrosis. The V617F mutation is a change of valine to phenylalanine at the 617 position. Janus kinases (JAKs) are non-receptor tyrosine kinases essential for the activation of signaling that is mediated by cytokine receptors lacking catalytic activity. These include receptors for erythropoietin, thrombopoietin, most interleukins and interferon. JAK2 mutations are significant because JAK2 plays a role in controlling production of blood cells from hematopoietic stem cells. The V617F mutation appears to make hematopoietic cells more sensitive to growth factors that need JAK2 for signal transduction, which include erythropoietin and thrombopoietin.[2]
- The MPL gene codes for a protein that acts as a receptor for thrombopoietin. A mutation in that gene, known as a W515 mutation, leads to the production of an abnormal thrombopoietin receptor protein, which results in the overproduction of abnormal megakaryocytes. The abnormal megakaryocytes stimulate other cells, the fibroblasts, to produce collagen in the bone marrow.[2]
References
- ↑ 1.0 1.1 Tefferi, A; Lasho, T L; Finke, C M; Knudson, R A; Ketterling, R; Hanson, C H; Maffioli, M; Caramazza, D; Passamonti, F; Pardanani, A (2014). "CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons". Leukemia. 28 (7): 1472–1477. doi:10.1038/leu.2014.3. ISSN 0887-6924.
- ↑ 2.0 2.1 2.2 2.3 Causes of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 7, 2016
- ↑ Baxter EJ, Scott LM, Campbell PJ; et al. (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet. 365 (9464): 1054–61. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101.
- ↑ Pikman Y, Lee BH, Mercher T; et al. (2006). "MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia". PLoS Med. 3 (7): e270. doi:10.1371/journal.pmed.0030270. PMC 1502153. PMID 16834459. Unknown parameter
|month=ignored (help)