Allelic expression imbalance of JAK2 V617F mutation in BCR-ABL negative myeloproliferative neoplasms

PLoS One. 2013;8(1):e52518. doi: 10.1371/journal.pone.0052518. Epub 2013 Jan 22.

Abstract

The discovery of a single point mutation in the JAK2 gene in patients with BCR/ABL-negative myeloproliferative neoplasms (MPNs) has not only brought new insights and pathogenesis, but also has made the diagnosis of MPNs much easier. Although, to date, several mechanisms for the contribution of single JAK2V617F point mutation to phenotypic diversity of MPNs have been suggested in multiple studies, but it is not clear how a unique mutation can cause the phenotypic diversity of MPNs. In this study, our results show that allelic expression imbalance of JAK2 V617F mutant frequently occurs and contributes to phenotypic diversity of BCR-ABL-negative MPNs. The proportion of JAK2 V617F mutant allele was significantly augmented in RNA levels as compared with genomic DNA differently by distinct MPNs subtypes. In detail, preferential expression of JAK2 mutant allele showed threefold increase from the cDNA compared with the genomic DNA from patients with essential thrombocythemia and twofold increase in polycythemia vera. In conclusion, allelic expression imbalance of JAK2 V617F mutant proposes another plausible mechanism for the contribution of single JAK2 point mutation to phenotypic diversity of MPNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles*
  • Asian People / genetics
  • Disease Progression
  • Female
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Gene Frequency
  • Genetic Markers / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / enzymology*
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / therapy
  • Point Mutation*
  • Treatment Outcome
  • Young Adult

Substances

  • Genetic Markers
  • Fusion Proteins, bcr-abl
  • Janus Kinase 2

Grants and funding

This work was supported by Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) (2011-0030034), Basic Science Research Program through NRF funded by the MEST (No. 2010-0024326) and a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, and Republic of Korea (A110367). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.