Design and application of a novel PNA probe for the detection at single cell level of JAK2V617F mutation in Myeloproliferative Neoplasms

BMC Cancer. 2013 Jul 18:13:348. doi: 10.1186/1471-2407-13-348.

Abstract

Background: Mutation(s) of the JAK2 gene (V617F) has been described in a significant proportion of Philadelphia negative Myeloproliferative Neoplasms (MPN) patients and its detection is now a cornerstone in the diagnostic algorithm.

Methods: We developed a novel assay based on peptide nucleic acid (PNA) technology coupled to immuno-fluorescence microscopy (PNA-FISH) for the specific detection at a single cell level of JAK2-mutation thus improving both the diagnostic resolution and the study of clonal prevalence.

Results: Using this assay we found a percentage of mutated CD34+ cells ranging from 40% to 100% in Polycythemia Vera patients, from 15% to 80% in Essential Thrombocythemia and from 25% to 100% in Primary Myelofibrosis. This method allows to distinguish, with a high degree of specificity, at single cell level, between CD34+ progenitor stem cells harbouring the mutated or the wild type form of JAK2 in NPM patients.

Conclusions: This method allows to identify multiple gene abnormalities which will be of paramount relevance to understand the pathophysiology and the evolution of any type of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Separation
  • Flow Cytometry
  • Humans
  • Janus Kinase 2 / genetics*
  • Microscopy, Fluorescence / methods*
  • Mutation*
  • Myeloproliferative Disorders / diagnosis*
  • Myeloproliferative Disorders / genetics*
  • Peptide Nucleic Acids*
  • Polymerase Chain Reaction

Substances

  • Peptide Nucleic Acids
  • Janus Kinase 2