title: Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha.
abstract: Imatinib and recombinant interferon alpha (rIFNalpha) can induce remission in polycythemia vera (PV) patients, but gauging the depth of responses has not been possible due to lack of a specific disease marker. We found that patients undergoing imatinib (n = 14) or rIFNalpha (n = 7) therapy remained strongly positive for V617F JAK2, although there was a significant reduction in the median percentage of mutant alleles that correlated with hematologic response (P = .001). Furthermore, individuals who achieved complete hematologic remission had lower levels of V617F than those who did not (P = .001). Of 9 imatinib-treated cases for whom pretreatment samples were available, 7 with no or partial hematologic responses showed a marginal increase (median, 1.2-fold; range, 1.0-1.5) in the percentage of V617F alleles on treatment, whereas the 2 patients who achieved complete hematologic remission showed a 2- to 3-fold reduction. Our data indicate that, although PV patients may benefit from imatinib or rIFNalpha, molecular responses are relatively modest.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom.
authors.forename: Amy V
authors.initials: AV
authors.lastname: Jones
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Katherine
authors.initials: K
authors.lastname: Waghorn
authors.forename: Claire
authors.initials: C
authors.lastname: Curtis
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreil
authors.forename: Katerina
authors.initials: K
authors.lastname: Zoi
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
authors.forename: Eva
authors.initials: E
authors.lastname: Lengfelder
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Chase
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007370:Interferon Type I / Q000008:administration & dosage*; D053614:Janus Kinase 2; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011087:Polycythemia Vera / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012074:Remission Induction / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015415:Biomarkers; D007370:Interferon Type I; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D011994:Recombinant Proteins; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2