Experimental therapy in myelofibrosis with myeloid metaplasia.
Myelofibrosis with myeloid metaplasia (MMM) is a Philadelphia chromosome-negative myeloproliferative disorder that is characterised by constitutional symptoms, progressive anaemia and extramedullary haematopoiesis. There are no curative therapies available for patients with MMM apart from stem cell transplantation, which is associated with significant morbidity and mortality, and for which most patients are not suitable candidates. Traditional pharmacological therapy of MMM has focused on the palliation of symptoms associated with myeloproliferation and correction of cytopoenias. Recently, new findings regarding the molecular basis of MMM and the pathogenesis of the associated bone marrow stromal reaction have provided both basic and clinical researchers with invaluable tools to develop effective targeted therapies for patients with MMM. Several novel treatment strategies are being investigated including antiangiogenic agents, signal transduction inhibitors, inhibitors of fibrogenesis and small-molecule inhibitors of the JAK2(V617F )mutation. This article reviews the current status of experimental novel therapies for MMM.
Verstovsek
Srdan
S
The University of Texas, Department of Leukemia, MD Anderson Cancer Center, USA.
Quintás-Cardama
Alfonso
A
Kantarjian
Hagop
H
Tefferi
Ayalew
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure; D002986:Clinical Trials as Topic; D002999:Clone Cells / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D051379:Mice; D009154:Mutation; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D017154:Stromal Cells / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D015507:Drugs, Investigational; D007155:Immunologic Factors; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D051231:Farnesyltranstransferase; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2