JAK2 in myeloproliferative disorders is not just another kinase

Ayalew Tefferi, D. Gary Gilliland

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


Myeloproliferative disorders (MPD) represent a subcategory of hematological malignancies and are characterized by a stem cell-derived clonal proliferation of myeloid cells including erythrocytes, platelets, and leucocytes. Traditionally, the term 'MPD' included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis with myeloid metaplasia (MMM). At present, these four disorders are referred to as 'classic' MPD and are distinguished from a spectrum of other MPD-like clinicopathologic entities that are operationally classified as 'atypical' MPD. The oncogenic mutations(s) in classic MPD are unknown except for CML, which is associated with an activating mutation (Bcr/Abl) of the gene encoding for the Abl cytoplasmic protein kinase (PTK). In the last 3 months, a somatic point mutation of JAK2 (JAK2V617F), the gene encoding for another cytoplasmic PTK was reported in the majority of patients with PV and approximately half of those with either ET or MMM. The same mutation was also found in a small number of patients with either atypical MPD or the myelodysplastic syndrome but not in normal controls, germline tissue including T lymphocytes, and patients with secondary erythrocytosis. In vitro, JAK2 V617F was associated with constitutive phosphorylation of JAK2 and its downstream effectors as well as induction of erythropoietin hypersensitivity in cell lines. In vivo, murine bone marrow transduced with a retrovirus containing JAK2V617F induced erythrocytosis in the transplanted mice. Taken together, these observations suggest that JAK2V617F is an acquired myeloid lineage-specific mutation that engenders a pathogenetic relevance for the PV phenotype in MPD.

Original languageEnglish (US)
Pages (from-to)4053-4056
Number of pages4
JournalCell Cycle
Issue number8
StatePublished - Aug 2005


  • Essential thrombocythemia
  • JAK2
  • Janus kinase
  • Mutation
  • Myelofibrsis
  • Myeloproliferative disorders
  • Polycythemia vera
  • Tyrosine kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


Dive into the research topics of 'JAK2 in myeloproliferative disorders is not just another kinase'. Together they form a unique fingerprint.

Cite this