Myelofibrosis

Alternative Names

  • Myelofibrosis with Myeloid Metaplasia
  • MMM

Associated Genes

Janus Kinase 2
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WHO-ICD-10 version:2010

Neoplasms

Neoplasms of uncertain or unknown behaviour

OMIM Number

254450

Mode of Inheritance

Somatic Mutation

Gene Map Locus

1p34.2,9p24.1,12q24.12,19p13.13

Description

Myelofibrosis is a chronic disorder arising from the neoplastic transformation of early hematopoietic stem cells, and is characterized by anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, and portal hypertension.  Myelofibrosis is a rare disorder that affects approximately 1 in 500,000 people worldwide.  It occurs most often in people between 50 and 70 years. 

Diagnosis is based on blood tests that show anemia and the misshapen, immature red blood cells.  Bone marrow biopsy is needed to confirm the diagnosis.  Treatment of myelofibrosis aims to delay the progression of the disorder and to relieve complications.  Drugs and other treatments lessen the severity of anemia, increase red blood cell production, and fight infections.  However, only stem cell transplantation can cure the disorder.  The median survival for patients with primary myelofibrosis is five years from onset, but variation is wide; some patients have a rapidly progressing disorder with short survival and some have a delay in initial diagnosis.  The common causes of death are infections, hemorrhage, cardiac failure, postsplenectomy mortality, and leukemic transformation.

Molecular Genetics

Mutations in the JAK2, MPL, CALR, and TET2 genes are associated with most cases of myelofibrosis.  Approximately 50-60% of patients with myelofibrosis have a gain-of-function mutation in the JAK2 gene, the JAK2 V617F mutation, which leads to increased cytokine responsiveness of myeloid cells.  Another 5-10% of the patients have somatic mutations of JAK2 exon 12 or activating mutations of the thrombopoietin receptor gene MPL.  Mutations in the gene encoding calreticulin (CALR) were present in the majority of patients who lacked mutations in JAK2 or MPL.

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
147796.G.1Lebanon Myeloproliferative DisorderNM_004972.3:c.1849G>TMahfouz et al. 2011 Study with 229 Myelo...

Other Reports

Saudi Arabia

Sheikha (2004) described four children (two girls and two boys) born to non-consanguineous parents, all of whom died of acute myelofibrosis during their first year of life.  The first child was a 2.5-month-old girl who presented with fever, cough, vomiting, diarrhea, and progressive pallor.  She had severe anemia and thrombocytopenia.  Her spleen progressively enlarged, and her cytopenia worsened rapidly.  She died at the age of 4-months.  The second child was a 1-month-old boy who was admitted to the hospital for right-sided ischiorectal abscess.  Two weeks later he had mild hepatosplenomegaly.  At the age of 3.5-months he developed hyperpyrexia, pancytopenia, moderate hepatomegaly, and massive splenomegaly.  He died at home at 8-months of age.  The third child was a 2-months old boy who was admitted to the hospital many times for infections, bleeding, fever, and blood transfusion.  He had severe pancytopenia with marked anisopoikilocytosis.  He died shortly after his first birthday.  The fourth child was admitted at 5-months of age with severe pancytopenia.  She was highly febrile and had epistaxis.  Her liver was 5 cm below the costal margin and her spleen well below the umbilicus.  Twelve days later, she died of severe, uncontrollable generalized bleeding and cardiopulmonary arrest.  

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