KEGG   DISEASE: MyelofibrosisHelp
Entry
H01605                      Disease                                

Name
Myelofibrosis
Description
Myelofibrosis (MF), one of the three classic Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs), is characterized by symptoms mainly derived from anemia and splenomegaly and constitutional symptoms and associated with a median survival around 6 years. Most MPN patients harbor an acquired mutation in the hemopoietic cells, the V617F mutation, located in the pseudokinase domain of the JAK2 gene. This mutation results in a gain of function, i.e., in the constitutive activation of the JAK-STAT pathway, which plays an important role in the proliferation, differentiation, and survival of the hemopoietic cells, as well as in the immune function. Besides, a minority of patients with MF (most of them negative for the JAK2 mutation) harbor other JAK-STAT-activating mutation, the MPL mutation, in the gene of the receptor of the thrombopoietin. Recently, mutations in the CALR gene have been described in 86% of cases with primary MF that are negative for JAK2 or MPL mutations. CALR mutation also showed cytokine independent growth of cells due to activation of STAT5 involved with the JAK-STAT pathway but its exact role in MPN remains to be clarified.
Category
Cancer
Brite
Human diseases [BR:br08402]
 Cancers
  Cancers of haematopoietic and lymphoid tissues
   H01605  Myelofibrosis
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Neoplasms of haematopoietic or lymphoid tissues
   Myeloproliferative neoplasms
    2A20  Non mast cell myeloproliferative neoplasms
     H01605  Myelofibrosis
BRITE hierarchy
Pathway
hsa04630  JAK-STAT signaling pathway
Gene
MPL [HSA:4352] [KO:K05082]
JAK2 [HSA:3717] [KO:K04447]
CALR [HSA:811] [KO:K08057]
Drug
Oxymetholone [DR:D00490]
Ruxolitinib phosphate [DR:D09960]
Comment
ICD-0-3: 9961/3 Primary myelofibrosis
Other DBs
ICD-11: 2A20.2
ICD-10: D47.4
MeSH: D055728
Reference
  Authors
Hobbs GS, Rampal RK
  Title
Clinical and molecular genetic characterization of myelofibrosis.
  Journal
Curr Opin Hematol 22:177-83 (2015)
DOI:10.1097/MOH.0000000000000122
Reference
  Authors
Cervantes F, Martinez-Trillos A
  Title
Myelofibrosis: an update on current pharmacotherapy and future directions.
  Journal
Expert Opin Pharmacother 14:873-84 (2013)
DOI:10.1517/14656566.2013.783019
Reference
PMID:26835366 (description, gene, drug)
  Authors
Singh NR
  Title
Genomic diversity in myeloproliferative neoplasms: focus on myelofibrosis.
  Journal
Transl Pediatr 4:107-15 (2015)
DOI:10.3978/j.issn.2224-4336.2015.03.06
Reference
PMID:25124313 (marker, drug)
  Authors
Tefferi A
  Title
Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management.
  Journal
Am J Hematol 89:915-25 (2014)
DOI:10.1002/ajh.23703
Reference
  Authors
Lasho TL, Pardanani A, McClure RF, Mesa RA, Levine RL, Gilliland DG, Tefferi A
  Title
Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time.
  Journal
Br J Haematol 135:683-7 (2006)
DOI:10.1111/j.1365-2141.2006.06348.x

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