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Genetics Home Reference: your guide to understanding genetic conditions
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Primary myelofibrosis

Reviewed December 2011

What is primary myelofibrosis?

Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis.

Initially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising.

Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.

Primary myelofibrosis is most commonly diagnosed in people aged 50 to 80 but can occur at any age.

How common is primary myelofibrosis?

Primary myelofibrosis is a rare condition that affects approximately 1 in 500,000 people worldwide.

What genes are related to primary myelofibrosis?

Mutations in the JAK2, MPL, and TET2 genes are associated with most cases of primary myelofibrosis. The TET2 gene provides instructions for making a protein whose function is unknown. The JAK2 and MPL genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells.

The proteins produced from the JAK2 and MPL genes are both part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The protein produced from the MPL gene, called thrombopoietin receptor, turns on (activates) the pathway, and the JAK2 protein transmits signals after activation. Through the JAK/STAT pathway, these two proteins promote the proliferation of blood cells, particularly a type of blood cell known as megakaryocytes.

Mutations in either the JAK2 gene or the MPL gene that are associated with primary myelofibrosis lead to overactivation of the JAK/STAT pathway. The abnormal activation of JAK/STAT signaling leads to overproduction of abnormal megakaryocytes, and these megakaryocytes stimulate another type of cell to release collagen. Collagen is a protein that normally provides structural support for the cells in the bone marrow. However, in primary myelofibrosis, the excess collagen forms scar tissue in the bone marrow.

Although mutations in the TET2 gene have been found in approximately 17 percent of people with primary myelofibrosis, it is unclear what role these mutations play in the development of the condition.

Many people with primary myelofibrosis do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition.

Related Gene(s)

Changes in these genes are associated with primary myelofibrosis.

  • IDH1
  • IDH2
  • JAK2
  • MPL
  • TET2

How do people inherit primary myelofibrosis?

This condition is generally not inherited but arises from gene mutations that occur after conception. This alteration is called a somatic mutation.

Where can I find information about diagnosis or management of primary myelofibrosis?

These resources address the diagnosis or management of primary myelofibrosis and may include treatment providers.

  • Genetic Testing Registry: Myelofibrosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0001815)
  • Merck Manual for Health Care Professionals: Primary Myelofibrosis (http://www.merckmanuals.com/professional/hematology_and_oncology/myeloproliferative_disorders/primary_myelofibrosis.html)
  • Myeloproliferative Neoplasm (MPN) Research Foundation: Primary Myelofibrosis (PMF) (http://www.mpnresearchfoundation.org/Primary-Myelofibrosis)

You might also find information on the diagnosis or management of primary myelofibrosis in Educational resources (http://www.ghr.nlm.nih.gov/condition/primary-myelofibrosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/primary-myelofibrosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about primary myelofibrosis?

You may find the following resources about primary myelofibrosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for primary myelofibrosis?

  • agnogenic myeloid metaplasia
  • chronic idiopathic myelofibrosis
  • idiopathic myelofibrosis
  • myelofibrosis with myeloid metaplasia
  • myeloid metaplasia

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about primary myelofibrosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding primary myelofibrosis?

agnogenic ; anemia ; bone marrow ; cell ; chronic ; collagen ; enlarged spleen ; fever ; fibrosis ; gene ; idiopathic ; inherited ; metaplasia ; mutation ; myeloid ; nucleus ; platelets ; proliferation ; protein ; receptor ; somatic mutation ; splenomegaly ; tissue ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Chaligné R, Tonetti C, Besancenot R, Roy L, Marty C, Mossuz P, Kiladjian JJ, Socié G, Bordessoule D, Le Bousse-Kerdilès MC, Vainchenker W, Giraudier S. New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition. Leukemia. 2008 Aug;22(8):1557-66. doi: 10.1038/leu.2008.137. Epub 2008 Jun 5. (http://www.ncbi.nlm.nih.gov/pubmed/18528423?dopt=Abstract)
  • Ciurea SO, Merchant D, Mahmud N, Ishii T, Zhao Y, Hu W, Bruno E, Barosi G, Xu M, Hoffman R. Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. Blood. 2007 Aug 1;110(3):986-93. Epub 2007 May 1. (http://www.ncbi.nlm.nih.gov/pubmed/17473062?dopt=Abstract)
  • Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, Cuker A, Wernig G, Moore S, Galinsky I, DeAngelo DJ, Clark JJ, Lee SJ, Golub TR, Wadleigh M, Gilliland DG, Levine RL. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006 Jul;3(7):e270. (http://www.ncbi.nlm.nih.gov/pubmed/16834459?dopt=Abstract)
  • Saint-Martin C, Leroy G, Delhommeau F, Panelatti G, Dupont S, James C, Plo I, Bordessoule D, Chomienne C, Delannoy A, Devidas A, Gardembas-Pain M, Isnard F, Plumelle Y, Bernard O, Vainchenker W, Najman A, Bellanné-Chantelot C; French Group of Familial Myeloproliferative Disorders. Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009 Aug 20;114(8):1628-32. doi: 10.1182/blood-2009-01-197525. Epub 2009 Jun 29. (http://www.ncbi.nlm.nih.gov/pubmed/19564637?dopt=Abstract)
  • Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Gangat N, Finke CM, Schwager S, Mullally A, Li CY, Hanson CA, Mesa R, Bernard O, Delhommeau F, Vainchenker W, Gilliland DG, Levine RL. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia. 2009 May;23(5):905-11. doi: 10.1038/leu.2009.47. Epub 2009 Mar 5. (http://www.ncbi.nlm.nih.gov/pubmed/19262601?dopt=Abstract)
  • Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010 Jun;24(6):1128-38. doi: 10.1038/leu.2010.69. Epub 2010 Apr 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20428194?dopt=Abstract)
  • Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol. 2005 Nov 20;23(33):8520-30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16293880?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2011
Published: September 1, 2014