title: Molecular responses and chromosomal aberrations in patients with polycythemia vera treated with peg-proline-interferon alpha-2b.
abstract: Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFNα-2b, AOP2014/P1101). Peg-proline-IFNα-2b treatment led to high response rates on both hematologic and molecular levels. Hematologic and molecular responses were achieved for 46 and 18 patients (90 and 35% of the whole cohort), respectively. Although interferon alpha (IFNα) is known to be an effective antineoplastic therapy for a long time, it is currently not well understood which genetic alterations influence therapeutic outcomes. Apart from somatic changes in specific genes, large chromosomal aberrations could impact responses to IFNα. Therefore, we evaluated the interplay of cytogenetic changes and IFNα responses in the PEGINVERA cohort. We performed high-resolution SNP microarrays to analyze chromosomal aberrations prior and during peg-proline-IFNα-2b therapy. Similar numbers and types of chromosomal aberrations in responding and non-responding patients were observed, suggesting that peg-proline-IFNα-2b responses are achieved independently of chromosomal aberrations. Furthermore, complete cytogenetic remissions were accomplished in three patients, of which two showed more than one chromosomal aberration. These results imply that peg-proline-IFNα-2b therapy is an effective drug for PV patients, possibly including patients with complex cytogenetic changes.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Nicole C C
authors.initials: NC
authors.lastname: Them
authors.forename: Klaudia
authors.initials: K
authors.lastname: Bagienski
authors.forename: Tiina
authors.initials: T
authors.lastname: Berg
authors.forename: Bettina
authors.initials: B
authors.lastname: Gisslinger
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.forename: Doris
authors.initials: D
authors.lastname: Chen
authors.forename: Veronika
authors.initials: V
authors.lastname: Buxhofer-Ausch
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
authors.forename: Ernst
authors.initials: E
authors.lastname: Schloegl
authors.forename: Guenther A
authors.initials: GA
authors.lastname: Gastl
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
authors.forename: Karin
authors.initials: K
authors.lastname: Strecker
authors.forename: Alexander
authors.initials: A
authors.lastname: Egle
authors.forename: Thomas
authors.initials: T
authors.lastname: Melchardt
authors.forename: Sonja
authors.initials: S
authors.lastname: Burgstaller
authors.forename: Ella
authors.initials: E
authors.lastname: Willenbacher
authors.forename: Oleh
authors.initials: O
authors.lastname: Zagrijtschuk
authors.forename: Christoph
authors.initials: C
authors.lastname: Klade
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002869:Chromosome Aberrations / Q000187:drug effects; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000187:drug effects; D055106:Genome-Wide Association Study; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011087:Polycythemia Vera / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D004247:DNA; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C417083:peginterferon alfa-2b