Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia.
Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (ie, BCR-ABL-negative) myeloproliferative disorder characterized by anemia, multiorgan extramedullary hematopoiesis, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Stem cell transplantation can be curative, but many patients either are not appropriate candidates or do not choose to accept the significant risks associated with transplantation. Current pharmacologic therapy has been beneficial mainly in terms of palliating disease-associated cytopenias, constitutional symptoms, splenomegaly, and other organ damage from excess myeloproliferation. Novel treatment strategies are under investigation, including targeted inhibition of JAK2(V617F), the activating tyrosine kinase point mutation present in about half of patients with MMM. In this article, we review both the old and new pharmacologic options for MMM.
Mesa
Ruben A
RA
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. mesa.ruben@mayo.edu
Quintás-Cardama
Alfonso
A
Verstovsek
Srdan
S
D000368:Aged; D000477:Alkylating Agents / Q000627:therapeutic use; D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000209:etiology; D018450:Disease Progression; D016503:Drug Delivery Systems; D015507:Drugs, Investigational / Q000627:therapeutic use; D004921:Erythropoietin / Q000627:therapeutic use; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008875:Middle Aged; D020125:Mutation, Missense; D010166:Palliative Care; D017354:Point Mutation; D055728:Primary Myelofibrosis / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013921:Thrombocytopenia / Q000188:drug therapy / Q000209:etiology
D000477:Alkylating Agents; D000964:Antimetabolites, Antineoplastic; D015507:Drugs, Investigational; D007155:Immunologic Factors; D047428:Protein Kinase Inhibitors; D004921:Erythropoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2