JAK2 in myeloproliferative disorders is not just another kinase

Ayalew Tefferi, D. Gary Gilliland

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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)1053-1056
Number of pages4
JournalCell Cycle
Volume4
Issue number8
StatePublished - Aug 2005

Fingerprint

Myeloproliferative Disorders
Gene encoding
Protein Kinases
Phosphotransferases
Phosphorylation
T-cells
Erythropoietin
Platelets
Stem cells
Polycythemia Vera
Bone
Cells
Tissue
Essential Thrombocythemia
Polycythemia
Primary Myelofibrosis
Mutation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
abl Genes
Myelodysplastic Syndromes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

JAK2 in myeloproliferative disorders is not just another kinase. / Tefferi, Ayalew; Gilliland, D. Gary.

In: Cell Cycle, Vol. 4, No. 8, 08.2005, p. 1053-1056.

Research output: Contribution to journalArticle

Tefferi, A & Gilliland, DG 2005, 'JAK2 in myeloproliferative disorders is not just another kinase', Cell Cycle, vol. 4, no. 8, pp. 1053-1056.
Tefferi, Ayalew ; Gilliland, D. Gary. / JAK2 in myeloproliferative disorders is not just another kinase. In: Cell Cycle. 2005 ; Vol. 4, No. 8. pp. 1053-1056.
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