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

   

Authors:	Quintas-Cardama, A.; Abdel-Wahab, O.; Manshouri, T.; Kilpivaara, O.; Cortes, J.; Roupe, A. L.; Zhang, S. J.; Harris, D.; Estrov, Z.; Kantarjian, H.; Levine, R. L.; Verstovsek, S.
Article Title:	Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon alpha-2a
Abstract:	Pegylated interferon alpha-2a (PEG-IFN-alpha-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-alpha-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 wildtype patients. These data demonstrate that PEG-IFN-alpha-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-alpha-2a.
Keywords:	myelofibrosis; chronic myelomonocytic leukemia; mutation; tyrosine; differentiation; hematopoietic stem-cells; disorders; kinase jak2; tet2; myeloproliferative neoplasms; myeloid malignancies
Journal Title:	Blood
Volume:	122
Issue:	6
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2013-08-08
Start Page:	893
End Page:	901
Language:	English
DOI:	10.1182/blood-2012-07-442012
ACCESSION:	WOS:000322879100012
PROVIDER:	wos
PMCID:	PMC3739035
PUBMED:	23782935
Notes:	--- - Article - "Source: Wos"

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