Myeloproliferative Neoplasms

Part of the series Contemporary Hematology pp 117-138


Conventional and Investigational Therapy for Primary Myelofibrosis

  • Giovanni BarosiAffiliated withUnit of Clinical Epidemiology and Centre for the Study of Myelofibrosis, IRCCS Policlinico San Matteo Foundation Email author 

* Final gross prices may vary according to local VAT.

Get Access


Primary myelofibrosis (PMF), also known as myelofibrosis with myeloid metaplasia or agnogenic myeloid metaplasia, is a clonal myeloproliferative neoplasm that, in patients with fully expressed disease, is characterized by profound remodeling of bone marrow architecture and derangement of hematopoiesis. Bone marrow appears with almost constant expanded population of megakaryocytes and clusters of dystrophic and dysmature elements, deposition of excessive amounts of collagen, and other extracellular matrix proteins resulting in marrow reticulin or collagen fibrosis, increase in microvessel density, and osteosclerosis. Specific hallmarks of hematopoiesis derangement consist in the aberrantly decreased expression of disease-associated surface receptors on hematopoietic stem cell, such as SDF-1 receptor CXCR4, TGF-β (beta) receptor, and TPO receptor MPL, associated with high levels of stromal molecules, like SDF-1, elastase, and metalloproteinases. These stem cell and microenvironmental alterations bring to disruption of bone marrow niches with ensuing mobilization and homing of neoplastic hematopoietic stem cells in new or reinitialized niches in the spleen and liver. These features result in extramedullary hematopoiesis (EMH) with splenomegaly, anemia with a leukoerythroblastic blood picture, and possible neutropenia and thrombocytopenia.


Primary myelofibrosis SDF-1 CXCR4 TGF-β (beta) JAK2V617F MPLW515L/K Androgens Nandrolone Fluoxymesterolone Methandrostenolone Oxymetolone Metenolone Danazol Erythropoietin rHuEpo Darbepoetin Thalidomide Anemia Transfusion-dependent anemia Symptomatic splenomegaly Leukemic transformation Pulmonary ­hypertension Erythropoiesis-stimulating agents EUMNET IWG-MRT Iron overload Deferoxamine Deferiprone Deferasirox Hydroxyurea Busulphan Interferon Pegylated interferon Splenic radiotherapy Splenectomy Portal vein thrombosis Post-splenectomy hepatomegaly 2-chlorodexoxyadenosine Liver radiotherapy Extramedullary hematopoiesis Abdominal radiotherapy Paraspinal extramedullary hematopoiesis Lenalidomide Pomalidomide Tipifarnib Bortezomib Vascular Endothelial Growth Factor Epigenetics Azacitidine Decitabine Vorinostat Givinostat