Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a

Alfonso Quintás-Cardama, Omar Abdel-Wahab, Taghi Manshouri, Outi Kilpivaara, Jorge Cortes, Anne Laure Roupie, Su Jiang Zhang, David Harris, Zeev Estrov, Hagop Kantarjian, Ross L. Levine, Srdan Verstovsek

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Pegylated interferon α-2a (PEG-IFN-α-2a) has previously been shown to induce hematologic and molecular responses in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Here we present a follow-up of a phase 2 trial with PEG-IFN-α-2a treatment in 43 PV and 40 ET patients with detailed molecular analysis. After a median follow-up of 42 months, complete hematologic response was achieved in 76% of patients with PV and 77% of those with ET. This was accompanied by complete molecular response (CMR) (ie, undetectable JAK2V617F) in 18% and 17%, of PV and ET patients, respectively. Serial sequencing of TET2, ASXL1, EZH2, DNMT3A, and IDH1/2 revealed that patients failing to achieve CMR had a higher frequency of mutations outside the Janus kinase–signal transducer and activator of transcription pathway and were more likely to acquire new mutations during therapy. Patients with both JAK2V617F and TET2 mutations at therapy onset had a higher JAK2V617F mutant allele burden and a less significant reduction in JAK2V617F allele burden compared with JAK2 mutant/TET2 wild-type patients. These data demonstrate that PEG-IFN-α-2a induces sustained CMR in a subset of PV or ET patients, and that genotypic context may influence clinical and molecular response to PEG-IFN-α-2a.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalBlood
Volume122
Issue number6
DOIs
StatePublished - Aug 8 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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