Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha.
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.
Jones
Amy V
AV
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom.
Silver
Richard T
RT
Waghorn
Katherine
K
Curtis
Claire
C
Kreil
Sebastian
S
Zoi
Katerina
K
Hochhaus
Andreas
A
Oscier
David
D
Metzgeroth
Georgia
G
Lengfelder
Eva
E
Reiter
Andreas
A
Chase
Andrew J
AJ
Cross
Nicholas C P
NC
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
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