title: Usefulness of quantitative assessment of JunB gene expression as a marker for monitoring chronic myeloid leukemia patients undergoing imatinib therapy.
abstract: JunB is a component of the activator protein 1 transcription factors and has been identified to be important in hematopoiesis. Transgenic mice lacking JunB expression develop myeloproliferative disease resembling human chronic myeloid leukemia (CML). JunB expression was significantly decreased in CML patients. We used real-time quantitative reverse transcription-polymerase chain reaction analysis to monitor both JunB and BCR-ABL expression during imatinib therapy. Nineteen patients were evaluated every 2 to 4 weeks, and their levels of JunB expression before therapy were significantly decreased compared with those of healthy individuals. After imatinib therapy, an increase in JunB expression was found in 5 patients, all of whom achieved a complete cytogenetic response (CCR) and molecular response (MR), with a decrease in BCR-ABL expression. JunB expression decreased to a very low level in 2 patients, both of whom showed progression to blast crisis. Variable JunB expression was found in the other 12 patients, and their outcomes were mostly driven by BCR-ABL levels. The patients with an increase in JunB expression were statistically more likely to achieve a major cytogenetic response (P = .045), CCR (P = .033), and MR (P = .033) than the group with no increase in JunB expression, and a durable response was observed. This study revealed that an increase in JunB expression is a good prognostic marker for predicting clinical response in CML patients treated with imatinib when such data are combined with an evaluation of BCR-ABL expression.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Liu
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Hsiao
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Yang
authors.forename: Ta-Chih
authors.initials: TC
authors.lastname: Liu
authors.forename: Chao-Song
authors.initials: CS
authors.lastname: Chang
authors.forename: Shih-Bin
authors.initials: SB
authors.lastname: Tseng
authors.forename: Huei-Jen
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Sheng-Fung
authors.initials: SF
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010879:Piperazines / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D016755:Proto-Oncogene Proteins c-jun; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl