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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Alleles
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Amino Acid Substitution
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Antineoplastic Agents / administration & dosage*
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Benzamides
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Biomarkers / blood
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Dose-Response Relationship, Drug
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Female
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Hematopoiesis / drug effects
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Hematopoiesis / genetics
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Humans
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Imatinib Mesylate
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Interferon Type I / administration & dosage*
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Janus Kinase 2
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Male
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Middle Aged
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Piperazines / administration & dosage*
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Polycythemia Vera / blood
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Polycythemia Vera / drug therapy*
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Polycythemia Vera / genetics
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Protein Kinase Inhibitors / administration & dosage*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / genetics
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics
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Pyrimidines / administration & dosage*
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Recombinant Proteins
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Remission Induction / methods
Substances
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Antineoplastic Agents
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Benzamides
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Biomarkers
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Interferon Type I
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Piperazines
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Pyrimidines
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Recombinant Proteins
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Imatinib Mesylate
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Protein-Tyrosine Kinases
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JAK2 protein, human
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Janus Kinase 2