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 in ICD-11 classification [BR:br08403]
02 Neoplasms
Neoplasms of haematopoietic or lymphoid tissues
Myeloproliferative neoplasms
2A20 Non mast cell myeloproliferative neoplasms
H01605 Myelofibrosis
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06518 JAK-STAT signaling
H01605 Myelofibrosis
Cellular process
nt06535 Efferocytosis
H01605 Myelofibrosis
