Published online before print December 12, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: jmoldx.2009.080114v1 11/1/49    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ma, W. Articles by Albitar, M. Search for Related Content PubMed PubMed Citation Articles by Ma, W. Articles by Albitar, M.

Journal of Molecular Diagnostics 2009, Vol. 11, No. 1
Copyright © 2009 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2009.080114

Mutation Profile of JAK2 Transcripts in Patients with Chronic Myeloproliferative Neoplasias

Wanlong Ma^*, Hagop Kantarjian, Xi Zhang^*, Chen-Hsiung Yeh^*, Zhong J. Zhang^*, Srdan Verstovsek and Maher Albitar^*

From the Hematopathology Department, * Quest Diagnostics Nichols Institute, San Juan Capistrano, California, and the Leukemia and Bioimmunotherapy Department, M.D. Anderson Cancer Center, University of Texas, Houston, Texas

Here, we describe the JAK2 mutation profile in a series of approximately 20,000 blood samples from patients with clinically suspected myeloproliferative neoplasias. Using a sensitive reverse transcription-PCR and direct sequencing approach on RNA rather than DNA, we detected JAK2 mutations in exons 12–15 in approximately 20% of these patients. We identified new mutations in addition to the known V617F and exon 12 mutations, which were the most common. Most of the novel mutations are located in the pseudokinase domain and therefore are expected to relieve the autoinhibitory function of this domain on JAK2 kinase activity. Our data suggest that molecular testing of JAK2 mutations should not be restricted to the V617F and exon 12 mutations, but perhaps should extend to most of the pseudokinase domain coding region as well. Furthermore, mutation screening using RNA is highly sensitive and could replace DNA-based testing because of the relative abundance of target transcripts and the ease in detecting deletion of the entire exon.