Primary Myelofibrosis

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This entry is adapted from https://medlineplus.gov/genetics/condition/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.

genetic conditions

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Subjects: Genetics & Heredity

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Peter Tang

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Entry Collection: MedlinePlus

Update Date: 04 Jan 2021

Table of Contents

1. Introduction

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.

2. Frequency

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

3. Causes

Mutations in the JAK2, MPL, CALR, and TET2 genes are associated with most cases of primary myelofibrosis. The JAK2 and MPL genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells. The CALR gene provides instructions for making a protein with multiple functions, including ensuring the proper folding of newly formed proteins and maintaining the correct levels of stored calcium in cells. The TET2 gene provides instructions for making a protein whose function is unknown.

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 a megakaryocyte.

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 CALR gene and the TET2 gene are relatively common in primary myelofibrosis, it is unclear how these mutations are involved in the development of the condition.

Some 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.

4. Inheritance

This condition is generally not inherited but arises from gene mutations that occur in early blood-forming cells after conception. These alterations are called somatic mutations.

5. Other Names for This Condition

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

References

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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 ofidiopathic myelofibrosis. Blood. 2007 Aug 1;110(3):986-93. Epub 2007 May 1. Citation on PubMed or Free article on PubMed Central
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Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J,Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P,Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT,Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S,McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M,Bowen D, Huntly BJP, Harrison CN, Cross NCP, Ron D, Vannucchi AM, Papaemmanuil E,Campbell PJ, Green AR. Somatic CALR mutations in myeloproliferative neoplasmswith nonmutated JAK2. N Engl J Med. 2013 Dec 19;369(25):2391-2405. doi:10.1056/NEJMoa1312542. Epub 2013 Dec 10. Citation on PubMed or Free article on PubMed Central
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 inmyelofibrosis with myeloid metaplasia. PLoS Med. 2006 Jul;3(7):e270. Citation on PubMed or Free article on PubMed Central
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; FrenchGroup of Familial Myeloproliferative Disorders. Analysis of the ten-eleventranslocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood. 2009Aug 20;114(8):1628-32. doi: 10.1182/blood-2009-01-197525. Epub 2009 Jun 29. Citation on PubMed
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, DelhommeauF, Vainchenker W, Gilliland DG, Levine RL. TET2 mutations and their clinicalcorrelates in polycythemia vera, essential thrombocythemia and myelofibrosis.Leukemia. 2009 May;23(5):905-11. doi: 10.1038/leu.2009.47. Epub 2009 Mar 5. Citation on PubMed or Free article on PubMed Central
Tefferi A. Novel mutations and their functional and clinical relevance inmyeloproliferative 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. Citation on PubMed or Free article on PubMed Central
Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J ClinOncol. 2005 Nov 20;23(33):8520-30. Review. Citation on PubMed

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Subjects: Genetics & Heredity

Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Peter Tang

View Times: 150

Entry Collection: MedlinePlus

Update Date: 04 Jan 2021

Table of Contents

1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

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1. Introduction

2. Frequency

3. Causes

3.1. The genes associated with Primary myelofibrosis

4. Inheritance

5. Other Names for This Condition

References

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