Technical Notes

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MPD Quest

(JAK 2 Mutation Analysis for Myeloproliferative disorders)

JAK2 is a somatic point mutation (V617F) in the conserved autoinhibitory pseudokinase as a result causing replacement of Valine to Phenylalanine amino acid at position 617 domain of the Janus kinase 2 (JAK2) protein, that intern cause activation of the JAK/STAT (Signal Transducers and Activators of Transcription) pathway eventually leading to myeloproliferation. The mutation causes constitutive activation of the kinase, with deregulated intracellular signaling, that mimics continuous hematopoietic growth factor stimulation. JAK-2 mutation is an important marker of the malignant clone & a useful diagnostic tool in Polycythemia Vera, Essential Thrombocythemia, Idiopathic Myelofibrosis & other myeloproliferative disorders. JAK2 mutation is reported in:
  • 74-97% cases of Polycythemia vera (PV),
  • 33-57% cases of Essential Thrombocythemia (ET) and
  • 35%-40% cases of Idiopathic Myelofibrosis (IMF)
The identification of the JAK2 mutation represents a major advance in our understanding of the molecular pathogenesis of myeloproliferative disorders. Mutation in JAK2 (V617F) has exhibited distinctive clinical manifestations and prognosis.
Much specific PCR is employed to detect somatic point mutation at the JAK 2 domain to confirm:
  • Diagnosis of PV, ET, and IMF
  • Clonal haematopoietic stem cell disorder
  • MPD in cases with high erythrocyte, leukocyte, or platelet counts
  • For evaluation of JAK2 targeted therapies that may soon be available

Methodology:

Patients DNA would be isolated, purified and subjected to PCR amplification using primers & Taqman probes. An additional amplification directed at GAPDH would be performed as a control for sample DNA quality.
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