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.
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Mechta-Grigoriou F, Gerald D, Yaniv M. The mammalian Jun proteins: redundancy and specificity. Oncogene. 2001;20:2378–2389.
Deng T, Karin M. JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Genes Dev. 1993;7:479–490.
Hsu JC, Cressman DE, Taub R. Promoter-specific trans-activation and inhibition mediated by JunB. Cancer Res. 1993;53:3789–3794.
Bakiri L, Lallemand D, Bossy-Wetzel E, Yaniv M. Cell cycle-dependent variations in c-Jun and JunB phosphorylation: a role in the control of cyclin D1 expression. EMBO J. 2000;19:2056–2068.
Passegué E, Wagner EF. JunB suppresses cell proliferation by transcriptional activation of p16INK4a expression. EMBO J.2000;19:2969–2979.
Szabowski A, Maas-Szabowski N, Andrecht S, et al. c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin. Cell. 2000;103:745–755.
Schreiber M, Kolbus A, Piu F, et al. Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev. 1999;13:607–619.
Shaulian E, Schreiber M, Piu F, Beeche M, Wagner EF, Karin M. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell. 2000;103:897–907.
Passegué E, Jochum W, Schorpp-Kistner M, Mohle-Steinlein U, Wagner EF. Chronic myeloid leukemia with increased granulocyte progenitors in mice lacking JunB expression in the myeloid lineage. Cell. 2001;104:21–32.
Szremska AP, Kenner L, Weisz E, et al. JunB inhibits proliferation and transformation in B-lymphoid cells. Blood. 2003;102:4159–4165.
Mao X, Orchard G, Lillington DM, Russell-Jones R, Young BD, Whittaker SJ. Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas. Blood. 2003;101:1513–1519.
Mathas S, Hinz M, Anagnostopoulos I, et al. Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-κB. EMBO J. 2002;21:4104–4113.
Yang MY, Liu TC, Chang JG, Lin PM, Lin SF. JunB gene expression inactivated by methylation in chronic myelogenous leukemia. Blood. 2003;101:3205–3211.
Savage DG, Antman KH. Imatinib mesylate: a new oral targeted therapy. N Engl J Med. 2002;346:683–693.
O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004.
Kantarjian H, Sawyers C, Hochhaus A. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346:645–652.
Talpaz M, Silver RT, Druker BJ. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: result of a phase 2 study. Blood. 2002;99:1928–1937.
Sawyers CL, Hochhaus A, Feldman E. Imatinib induces hematologic and cytogenetic responses in patients with chronic myeloid leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002;99:3530–3539.
Merx K, Muller MC, Kreil S, et al. Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon αlpha. Leukemia. 2002;16:1579–1583.
Wang L, Pearson K, Pillitteri L, Ferguson JE, Clark RE. Serial monitoring of BCR-ABL by peripheral blood real-time polymerase chain reaction predicts the marrow cytogenetic response to imatinib mesylate in chronic myeloid leukaemia. Br J Haematol. 2002;118:771–777.
Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;35:1423–1432.
Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001;293:876–880.
Barthe C, Cony-Makhoul P, Melo JV, Mahon JR. Roots of clinical resistance to STI-571 cancer therapy. Science. 2001;293:2163.
Gambacorti-Passerini C, Barni R, le Coutre P, et al. Role of ±1 acid glycoprotein in the in vivo resistance of human BCR-ABL+ leukemic cells to the Abl inhibitor STI571. J Natl Cancer Inst. 2000;92:1641–1650.
Honda H, Ushijima T, Wakazono K, et al. Acquired loss of p53 induces blastic transformation in p210bcr/abl-expressing hemato-poietic cells: a transgenic study for blast crisis of human CML. Blood. 2000;95:1144–1150.
Preudhomme C, Revillion F, Merlat A, et al. Detection of BCR-ABL transcripts in chronic myeloid leukemia (CML) using a ‘real time’ quantitative RT-PCR assay. Leukemia. 1999;13:957–964.
Eder M, Battmer K, Kafert S, Stucki A, Ganser A, Hertenstein B. Monitoring of BCR-ABL expression using real-time RT-PCR in CML after bone marrow or peripheral blood stem cell transplantation. Leukemia. 1999;13:1383–1389.
Goldman JM, Melo JV. Chronic myeloid leukemia: advances in biology and new approaches to treatment. N Engl J Med. 2003;349:1451–1464.
Deininger MWN, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96:3343–3356.
Barnes DJ, Melo JV. Management of chronic myeloid leukemia: targets for molecular therapy. Semin Hematol. 2003;40:34–49.
Raitano AB, Halpern JR, Hambuch TM, Sawyers CL. The Bcr-Abl leukemia oncogene activates Jun kinase and requires Jun for transformation. Proc Natl Acad Sci U S A. 1995;92:11746–11750.
Burgess GS, Williamson EA, Cripe LD, et al. Regulation of the c-jun gene in p210 BCR-ABL transformed cells corresponds with activity of JNK, the c-jun N-terminal kinase. Blood. 1998;92:2450–2460.
Calabretta B, Perrotti D. The biology of CML blast crisis. Blood. 2004;103:4010–4022.
Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood. 2001;98:2039–2342.
Goldman JM, Marin D, Olavarria E, Apperley JF. Clinical decisions for chronic myeloid leukemia in the imatinib era. Semin Hematol. 2003;40(suppl 2):98–103.
Hasford J, Pfirrmann M, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa: Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst. 1998;90:850–858.
Kantarjian HM, Talpaz M, Cortes J, et al. Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia. Clin Cancer Res. 2003;9:160–166.
Hughes T, Branford S. Molecular monitoring of chronic myeloid leukemia. Semin Hematol. 2003;40:62–68.
Passegué E, Wagner EF, Weissman IL. JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells. Cell. 2004;119:431–443.
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Liu, Y., Hsiao, H., Chang, J. et al. Usefulness Of Quantitative Assessment of Junb Gene Expression as a Marker for Monitoring Chronic Myeloid Leukemia Patients Undergoing Imatinib Therapy. Int J Hematol 84, 425–431 (2006). https://doi.org/10.1532/IJH97.A10514
- Imatinib mesylate
- Real-time quantitative RT-PCR
- Chronic myeloid leukemia