How I treat myelofibrosis

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Abstract

It is currently assumed that myelofibrosis (MF) originates from acquired mutations that target the hematopoietic stem cell and induce dysregulation of kinase signaling, clonal myeloproliferation, and abnormal cytokine expression. These pathogenetic processes are interdependent and also individually contributory to disease phenotype-bone marrow stromal changes, extramedullary hematopoiesis, ineffective erythropoiesis, and constitutional symptoms. Molecular pathogenesis of MF is poorly understood despite a growing list of resident somatic mutations that are either functionally linked to Janus kinase (JAK)-signal transducer and activator of transcription hyperactivation (eg JAK2, MPL, and LNK mutations) or possibly involved in epigenetic dysregulation of transcription (TET2, ASXL1, or EZH2 mutations). Current prognostication in primary MF is based on the Dynamic International Prognostic Scoring System-plus model, which uses 8 independent predictors of inferior survival to classify patients into low, intermediate 1, intermediate 2, and high-risk disease groups; corresponding median survivals are estimated at 15.4, 6.5, 2.9, and 1.3 years. Such information is used to plan a risk-adapted treatment strategy for the individual patient, which might include observation alone, conventional or investigational (eg, JAK inhibitors, pomalidomide) drug therapy, allogenic stem cell transplantation with reduced- or conventional-intensity conditioning, splenectomy, or radiotherapy. I discuss these treatment approaches in the context of who should get what and when.

Original languageEnglish (US)
Pages (from-to)3494-3504
Number of pages11
JournalBlood
Volume117
Issue number13
DOIs
StatePublished - Mar 31 2011

Fingerprint

Janus Kinases
Primary Myelofibrosis
Transcription
Stem cells
Drug therapy
Mutation
Radiotherapy
Transducers
Bone
Phosphotransferases
Bone Marrow Diseases
Extramedullary Hematopoiesis
Cytokines
Survival
Erythropoiesis
Stem Cell Transplantation
Splenectomy
Hematopoietic Stem Cells
Epigenomics
Observation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

How I treat myelofibrosis. / Tefferi, Ayalew.

In: Blood, Vol. 117, No. 13, 31.03.2011, p. 3494-3504.

Research output: Contribution to journalArticle

Tefferi, Ayalew. / How I treat myelofibrosis. In: Blood. 2011 ; Vol. 117, No. 13. pp. 3494-3504.
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