• This record comes from PubMed

Antigens in chronic myeloid leukemia: implications for vaccine development

. 2011 Dec ; 60 (12) : 1655-68. [epub] 20111028

Language English Country Germany Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't, Review

Treatment with imatinib mesylate and other tyrosine kinase inhibitors (TKI) revolutionized the therapy of chronic myeloid leukemia (CML). However, it alone does not cure this disease. Moreover, some patients develop resistance or adverse effects to this therapy. As successful treatment of a portion of CML patients by hematopoietic stem cell transplantation (HSCT) suggests the importance of immune mechanisms in the elimination of leukemic cells, including leukemia stem cells, TKI administration or HSCT might be combined with vaccination to cure CML patients. However, antigens implicated in the immune responses have not yet been sufficiently identified. Therefore, in this report, we compiled and characterized a list of 165 antigens associated with CML (CML-Ag165) and analyzed the expression of the corresponding genes in CML phases, subpopulations of leukemic cells, and CML-derived cell lines using available datasets from microarray transcriptional-profiling studies. From the CML-Ag165 list, we selected antigens most suitable for vaccine development and evaluated their appropriate characteristics.

See more in PubMed

Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood. 2009;113:1619–1630. doi: 10.1182/blood-2008-03-144790. PubMed DOI PMC

Savona M, Talpaz M. Getting to the stem of chronic myeloid leukaemia. Nat Rev Cancer. 2008;8:341–350. doi: 10.1038/nrc2368. PubMed DOI

Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol. 2002;107:76–94. doi: 10.1159/000046636. PubMed DOI

Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351:657–667. doi: 10.1056/NEJMoa040258. PubMed DOI

Gangemi R, Paleari L, Orengo AM, Cesario A, Chessa L, Ferrini S, Russo P. Cancer stem cells: a new paradigm for understanding tumor growth and progression and drug resistance. Curr Med Chem. 2009;16:1688–1703. doi: 10.2174/092986709788186147. PubMed DOI

Pinilla-Ibarz J, Shah B, Dubovsky JA. The biological basis for immunotherapy in patients with chronic myelogenous leukemia. Cancer Control. 2009;16:141–152. PubMed

Brauer KM, Werth D, von Schwarzenberg K, Bringmann A, Kanz L, Grunebach F, Brossart P. BCR-ABL activity is critical for the immunogenicity of chronic myelogenous leukemia cells. Cancer Res. 2007;67:5489–5497. doi: 10.1158/0008-5472.CAN-07-0302. PubMed DOI

Scheich F, Duyster J, Peschel C, Bernhard H. The immunogenicity of Bcr-Abl expressing dendritic cells is dependent on the Bcr-Abl kinase activity and dominated by Bcr-Abl regulated antigens. Blood. 2007;110:2556–2560. doi: 10.1182/blood-2007-01-071001. PubMed DOI

Rezvani K. Peptide vaccine therapy for leukemia. Int J Hematol. 2011;93:274–280. doi: 10.1007/s12185-011-0781-3. PubMed DOI

Dennis G, Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol. 2003;4:3. doi: 10.1186/gb-2003-4-5-p3. PubMed DOI

Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57. doi: 10.1038/nprot.2008.211. PubMed DOI

Saeed AI, Sharov V, White J, et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques. 2003;34:374–378. PubMed

Papadopoulos KP, Suciu-Foca N, Hesdorffer CS, Tugulea S, Maffei A, Harris PE. Naturally processed tissue- and differentiation stage-specific autologous peptides bound by HLA class I and II molecules of chronic myeloid leukemia blasts. Blood. 1997;90:4938–4946. PubMed

Knights AJ, Weinzierl AO, Flad T, Guinn BA, Mueller L, Mufti GJ, Stevanovic S, Pawelec G. A novel MHC-associated proteinase 3 peptide isolated from primary chronic myeloid leukaemia cells further supports the significance of this antigen for the immunotherapy of myeloid leukaemias. Leukemia. 2006;20:1067–1072. doi: 10.1038/sj.leu.2404234. PubMed DOI

Caballero OL, Chen YT. Cancer/testis (CT) antigens: potential targets for immunotherapy. Cancer Sci. 2009;100:2014–2021. doi: 10.1111/j.1349-7006.2009.01303.x. PubMed DOI PMC

Greiner J, Schmitt M. Leukemia-associated antigens as target structures for a specific immunotherapy in chronic myeloid leukemia. Eur J Haematol. 2008;80:461–468. doi: 10.1111/j.1600-0609.2008.01053.x. PubMed DOI

Vonka V. Immunotherapy of chronic myeloid leukemia: present state and future prospects. Immunotherapy. 2010;2:227–241. doi: 10.2217/imt.10.2. PubMed DOI

Jaras M, Johnels P, Hansen N, et al. Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. Proc Natl Acad Sci USA. 2010;107:16280–16285. doi: 10.1073/pnas.1004408107. PubMed DOI PMC

Yong AS, Stephens N, Weber G, et al. Improved outcome following allogeneic stem cell transplantation in chronic myeloid leukemia is associated with higher expression of BMI-1 and immune responses to BMI-1 protein. Leukemia. 2011;25:629–637. doi: 10.1038/leu.2010.325. PubMed DOI PMC

Grunebach F, Mirakaj V, Mirakaj V, Muller MR, Brummendorf T, Brossart P. BCR-ABL is not an immunodominant antigen in chronic myelogenous leukemia. Cancer Res. 2006;66:5892–5900. doi: 10.1158/0008-5472.CAN-05-2868. PubMed DOI

Drexler HG, MacLeod RA, Uphoff CC. Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia. Leuk Res. 1999;23:207–215. doi: 10.1016/S0145-2126(98)00171-4. PubMed DOI

Smith BD, Kasamon YL, Kowalski J, et al. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res. 2010;16:338–347. doi: 10.1158/1078-0432.CCR-09-2046. PubMed DOI PMC

Andersson A, Eden P, Lindgren D, et al. Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations. Leukemia. 2005;19:1042–1050. doi: 10.1038/sj.leu.2403749. PubMed DOI

Schmidt S, Gastl G, Wolf D. Possible role for gene expression profiling in predicting responses to conventional or targeted drugs in patients with chronic myeloid leukemia. Leuk Lymphoma. 2008;49:643–647. doi: 10.1080/10428190801896194. PubMed DOI

Yong AS, Melo JV. The impact of gene profiling in chronic myeloid leukaemia. Best Pract Res Clin Haematol. 2009;22:181–190. doi: 10.1016/j.beha.2009.04.002. PubMed DOI

Diaz-Blanco E, Bruns I, Neumann F, et al. Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase. Leukemia. 2007;21:494–504. doi: 10.1038/sj.leu.2404549. PubMed DOI

Crossman LC, Mori M, Hsieh YC, et al. In chronic myeloid leukemia white cells from cytogenetic responders and non-responders to imatinib have very similar gene expression signatures. Haematologica. 2005;90:459–464. PubMed

Yong AS, Szydlo RM, Goldman JM, Apperley JF, Melo JV. Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML. Blood. 2006;107:205–212. doi: 10.1182/blood-2005-05-2155. PubMed DOI

Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 2006;103:2794–2799. doi: 10.1073/pnas.0510423103. PubMed DOI PMC

Lemoli RM, Salvestrini V, Bianchi E, et al. Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34− cell population with intrinsic resistance to imatinib. Blood. 2009;114:5191–5200. doi: 10.1182/blood-2008-08-176016. PubMed DOI

McWeeney SK, Pemberton LC, Loriaux MM, et al. A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib. Blood. 2010;115:315–325. doi: 10.1182/blood-2009-03-210732. PubMed DOI PMC

Burguillo FJ, Martin J, Barrera I, Bardsley WG. Meta-analysis of microarray data: the case of imatinib resistance in chronic myelogenous leukemia. Comput Biol Chem. 2010;34:184–192. doi: 10.1016/j.compbiolchem.2010.06.003. PubMed DOI

Liu R, Mitchell DA. Survivin as an immunotherapeutic target for adult and pediatric malignant brain tumors. Cancer Immunol Immunother. 2010;59:183–193. doi: 10.1007/s00262-009-0757-9. PubMed DOI PMC

Sturrock AB, Franklin KF, Rao G, Marshall BC, Rebentisch MB, Lemons RS, Hoidal JR. Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener’s granulomatosis autoantigen. J Biol Chem. 1992;267:21193–21199. PubMed

Dengler R, Munstermann U, al-Batran S, Hausner I, Faderl S, Nerl C, Emmerich B. Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells. Br J Haematol. 1995;89:250–257. doi: 10.1111/j.1365-2141.1995.tb03297.x. PubMed DOI

Hosen N, Sonoda Y, Oji Y, et al. Very low frequencies of human normal CD34+ haematopoietic progenitor cells express the Wilms’ tumour gene WT1 at levels similar to those in leukaemia cells. Br J Haematol. 2002;116:409–420. doi: 10.1046/j.1365-2141.2002.03261.x. PubMed DOI

Yong AS, Keyvanfar K, Eniafe R, Savani BN, Rezvani K, Sloand EM, Goldman JM, Barrett AJ. Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy. Leukemia. 2008;22:1721–1727. doi: 10.1038/leu.2008.161. PubMed DOI PMC

Maxwell CA, McCarthy J, Turley E. Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions? J Cell Sci. 2008;121:925–932. doi: 10.1242/jcs.022038. PubMed DOI

Greiner J, Ringhoffer M, Taniguchi M, et al. Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemia-associated antigen in acute and chronic myeloid leukemia. Exp Hematol. 2002;30:1029–1035. doi: 10.1016/S0301-472X(02)00874-3. PubMed DOI

Giannopoulos K, Dmoszynska A, Kowal M, et al. Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia. Leukemia. 2010;24:798–805. doi: 10.1038/leu.2010.29. PubMed DOI

Watari K, Tojo A, Nagamura-Inoue T, Nagamura F, Takeshita A, Fukushima T, Motoji T, Tani K, Asano S. Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene. FEBS Lett. 2000;466:367–371. doi: 10.1016/S0014-5793(00)01112-1. PubMed DOI

Oehler VG, Guthrie KA, Cummings CL, et al. The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells. Blood. 2009;114:3299–3308. doi: 10.1182/blood-2008-07-170282. PubMed DOI PMC

Kanojia D, Garg M, Saini S, Agarwal S, Kumar R, Suri A. Sperm associated antigen 9 expression and humoral response in chronic myeloid leukemia. Leuk Res. 2010;34:858–863. doi: 10.1016/j.leukres.2010.01.017. PubMed DOI

Hofmann S, Greiner J. Immunogenic antigens as therapeutic targets against myeloid leukaemic cells. Leuk Res. 2010;34:850–851. doi: 10.1016/j.leukres.2010.03.013. PubMed DOI

Karthigeyan D, Prasad SB, Shandilya J, Agrawal S, Kundu TK. Biology of aurora A kinase: implications in cancer manifestation and therapy. Med Res Rev. 2011;31:757–793. PubMed

Ochi T, Fujiwara H, Suemori K, Azuma T, Yakushijin Y, Hato T, Kuzushima K, Yasukawa M. Aurora-A kinase: a novel target of cellular immunotherapy for leukemia. Blood. 2009;113:66–74. doi: 10.1182/blood-2008-06-164889. PubMed DOI

Cammareri P, Scopelliti A, Todaro M, et al. Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res. 2010;70:4655–4665. doi: 10.1158/0008-5472.CAN-09-3953. PubMed DOI

Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423:255–260. doi: 10.1038/nature01572. PubMed DOI

Mohty M, Yong AS, Szydlo RM, Apperley JF, Melo JV. The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood. 2007;110:380–383. doi: 10.1182/blood-2006-12-065599. PubMed DOI

Rizo A, Horton SJ, Olthof S, et al. BMI1 collaborates with BCR-ABL in leukemic transformation of human CD34+ cells. Blood. 2010;116:4621–4630. doi: 10.1182/blood-2010-02-270660. PubMed DOI

Ross DM, Hughes TP, Melo JV. Do we have to kill the last CML cell? Leukemia. 2011;25:193–200. doi: 10.1038/leu.2010.197. PubMed DOI

Wu CJ (2008) Immunologic targeting of the cancer stem cell. In: The Stem Cell Research Community (ed) StemBook. doi:10.3824/stembook.1.21.1, http://www.stembook.org

Chen CI, Maecker HT, Lee PP. Development and dynamics of robust T-cell responses to CML under imatinib treatment. Blood. 2008;111:5342–5349. doi: 10.1182/blood-2007-12-128397. PubMed DOI PMC

Chen YT, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA. 1997;94:1914–1918. doi: 10.1073/pnas.94.5.1914. PubMed DOI PMC

Gnjatic S, Nishikawa H, Jungbluth AA, Gure AO, Ritter G, Jager E, Knuth A, Chen YT, Old LJ. NY-ESO-1: review of an immunogenic tumor antigen. Adv Cancer Res. 2006;95:1–30. doi: 10.1016/S0065-230X(06)95001-5. PubMed DOI

Lin YW, Beharry ZM, Hill EG, et al. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010;115:824–833. doi: 10.1182/blood-2009-07-233445. PubMed DOI PMC

Hu XF, Li J, Vandervalk S, Wang Z, Magnuson NS, Xing PX. PIM-1-specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis. J Clin Invest. 2009;119:362–375. PubMed PMC

Eichmann A, Yuan L, Breant C, Alitalo K, Koskinen PJ. Developmental expression of pim kinases suggests functions also outside of the hematopoietic system. Oncogene. 2000;19:1215–1224. doi: 10.1038/sj.onc.1203355. PubMed DOI

Fontana S, Alessandro R, Barranca M, Giordano M, Corrado C, Zanella-Cleon I, Becchi M, Kohn EC, De Leo G. Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines. J Proteome Res. 2007;6:4330–4342. doi: 10.1021/pr0704128. PubMed DOI

Steidl U, Kronenwett R, Rohr UP, et al. Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow-derived and circulating human CD34+ hematopoietic stem cells. Blood. 2002;99:2037–2044. doi: 10.1182/blood.V99.6.2037. PubMed DOI

Ng YY, van Kessel B, Lokhorst HM, Baert MR, van den Burg CM, Bloem AC, Staal FJ. Gene-expression profiling of CD34+ cells from various hematopoietic stem-cell sources reveals functional differences in stem-cell activity. J Leukoc Biol. 2004;75:314–323. doi: 10.1189/jlb.0603287. PubMed DOI

Zheng C, Li L, Haak M, et al. Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. Leukemia. 2006;20:1028–1034. doi: 10.1038/sj.leu.2404227. PubMed DOI

Yong AS, Rezvani K, Savani BN, Eniafe R, Mielke S, Goldman JM, Barrett AJ. High PR3 or ELA2 expression by CD34+ cells in advanced-phase chronic myeloid leukemia is associated with improved outcome following allogeneic stem cell transplantation and may improve PR1 peptide-driven graft-versus-leukemia effects. Blood. 2007;110:770–775. doi: 10.1182/blood-2007-02-071738. PubMed DOI PMC

Giehl M, Fabarius A, Frank O, Hochhaus A, Hafner M, Hehlmann R, Seifarth W. Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability. Leukemia. 2005;19:1192–1197. doi: 10.1038/sj.leu.2403779. PubMed DOI

Patel H, Gordon MY. Abnormal centrosome-centriole cycle in chronic myeloid leukaemia? Br J Haematol. 2009;146:408–417. doi: 10.1111/j.1365-2141.2009.07772.x. PubMed DOI

Gerber JM, Qin L, Kowalski J, et al. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011;86:31–37. doi: 10.1002/ajh.21915. PubMed DOI PMC

Mumprecht S, Matter M, Pavelic V, Ochsenbein AF. Imatinib mesylate selectively impairs expansion of memory cytotoxic T cells without affecting the control of primary viral infections. Blood. 2006;108:3406–3413. doi: 10.1182/blood-2006-04-018705. PubMed DOI

Wolf D, Tilg H, Rumpold H, Gastl G, Wolf AM. The kinase inhibitor imatinib—an immunosuppressive drug? Curr Cancer Drug Targets. 2007;7:251–258. doi: 10.2174/156800907780618293. PubMed DOI

Kim PS, Lee PP, Levy D. Dynamics and potential impact of the immune response to chronic myelogenous leukemia. PLoS Comput Biol. 2008;4:e1000095. doi: 10.1371/journal.pcbi.1000095. PubMed DOI PMC

Barrett J, Rezvani K. Immunotherapy: can we include vaccines with stem-cell transplantation? Nat Rev Clin Oncol. 2009;6:503–505. doi: 10.1038/nrclinonc.2009.115. PubMed DOI

Plimack ER, Kantarjian HM, Issa JP. Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma. 2007;48:1472–1481. doi: 10.1080/10428190701471981. PubMed DOI

Coral S, Sigalotti L, Gasparollo A, Cattarossi I, Visintin A, Cattelan A, Altomonte M, Maio M. Prolonged upregulation of the expression of HLA class I antigens and costimulatory molecules on melanoma cells treated with 5-aza-2′-deoxycytidine (5-AZA-CdR) J Immunother. 1999;22:16–24. doi: 10.1097/00002371-199901000-00003. PubMed DOI

Adair SJ, Hogan KT. Treatment of ovarian cancer cell lines with 5-aza-2′-deoxycytidine upregulates the expression of cancer-testis antigens and class I major histocompatibility complex-encoded molecules. Cancer Immunol Immunother. 2009;58:589–601. doi: 10.1007/s00262-008-0582-6. PubMed DOI PMC

Goodyear O, Agathanggelou A, Novitzky-Basso I, et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 2010;116:1908–1918. doi: 10.1182/blood-2009-11-249474. PubMed DOI

Fioretti D, Iurescia S, Fazio VM, Rinaldi M. DNA vaccines: developing new strategies against cancer. J Biomed Biotechnol. 2010;2010:174378. doi: 10.1155/2010/174378. PubMed DOI PMC

Chaise C, Buchan SL, Rice J, et al. DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance. Blood. 2008;112:2956–2964. doi: 10.1182/blood-2008-02-137695. PubMed DOI

Ling M, Wen YJ, Lim SH. Prevalence of antibodies against proteins derived from leukemia cells in patients with chronic myeloid leukemia. Blood. 1998;92:4764–4770. PubMed

Wu CJ, Yang XF, McLaughlin S, et al. Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia. J Clin Invest. 2000;106:705–714. doi: 10.1172/JCI10196. PubMed DOI PMC

Greiner J, Ringhoffer M, Taniguchi M, Hauser T, Schmitt A, Dohner H, Schmitt M. Characterization of several leukemia-associated antigens inducing humoral immune responses in acute and chronic myeloid leukemia. Int J Cancer. 2003;106:224–231. doi: 10.1002/ijc.11200. PubMed DOI

Guinn BA, Bland EA, Lodi U, Liggins AP, Tobal K, Petters S, Wells JW, Banham AH, Mufti GJ. Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia. Biochem Biophys Res Commun. 2005;335:1293–1304. doi: 10.1016/j.bbrc.2005.08.024. PubMed DOI

Takahashi H, Furukawa T, Yano T, et al. Identification of an overexpressed gene, HSPA4L, the product of which can provoke prevalent humoral immune responses in leukemia patients. Exp Hematol. 2007;35:1091–1099. doi: 10.1016/j.exphem.2007.03.015. PubMed DOI

Biernacki MA, Marina O, Zhang W, et al. Efficacious immune therapy in chronic myelogenous leukemia (CML) recognizes antigens that are expressed on CML progenitor cells. Cancer Res. 2010;70:906–915. doi: 10.1158/0008-5472.CAN-09-2303. PubMed DOI PMC

Zou L, Wu Y, Pei L, et al. Identification of leukemia-associated antigens in chronic myeloid leukemia by proteomic analysis. Leuk Res. 2005;29:1387–1391. doi: 10.1016/j.leukres.2005.04.021. PubMed DOI

Adams SP, Sahota SS, Mijovic A, Czepulkowski B, Padua RA, Mufti GJ, Guinn BA. Frequent expression of HAGE in presentation chronic myeloid leukaemias. Leukemia. 2002;16:2238–2242. doi: 10.1038/sj.leu.2402732. PubMed DOI

Schmitt M, Li L, Giannopoulos K, et al. Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules. Exp Hematol. 2006;34:1709–1719. doi: 10.1016/j.exphem.2006.07.009. PubMed DOI

Luetkens T, Schafhausen P, Uhlich F, et al. Expression, epigenetic regulation, and humoral immunogenicity of cancer-testis antigens in chronic myeloid leukemia. Leuk Res. 2010;34:1647–1655. doi: 10.1016/j.leukres.2010.03.039. PubMed DOI

Lim SH, Austin S, Owen-Jones E, Robinson L. Expression of testicular genes in haematological malignancies. Br J Cancer. 1999;81:1162–1164. doi: 10.1038/sj.bjc.6690824. PubMed DOI PMC

Martinez A, Olarte I, Mergold MA, et al. mRNA expression of MAGE-A3 gene in leukemia cells. Leuk Res. 2007;31:33–37. doi: 10.1016/j.leukres.2006.05.009. PubMed DOI

Paydas S, Tanriverdi K, Yavuz S, Seydaoglu G. PRAME mRNA levels in cases with chronic leukemia: clinical importance and review of the literature. Leuk Res. 2007;31:365–369. doi: 10.1016/j.leukres.2006.06.022. PubMed DOI

Zhang Y, Wang Z, Liu H, Giles FJ, Lim SH. Pattern of gene expression and immune responses to Semenogelin 1 in chronic hematologic malignancies. J Immunother. 2003;26:461–467. doi: 10.1097/00002371-200311000-00001. PubMed DOI

Wang Z, Zhang Y, Mandal A, Zhang J, Giles FJ, Herr JC, Lim SH. The spermatozoa protein, SLLP1, is a novel cancer-testis antigen in hematologic malignancies. Clin Cancer Res. 2004;10:6544–6550. doi: 10.1158/1078-0432.CCR-04-0911. PubMed DOI

Wang Z, Zhang Y, Liu H, Salati E, Chiriva-Internati M, Lim SH. Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies. Blood. 2003;101:955–960. doi: 10.1182/blood-2002-06-1930. PubMed DOI

Sanchez-Garcia I, Grutz G. Tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL2. Proc Natl Acad Sci USA. 1995;92:5287–5291. doi: 10.1073/pnas.92.12.5287. PubMed DOI PMC

Nosaka T, Kitamura T. Pim-1 expression is sufficient to induce cytokine independence in murine hematopoietic cells, but is dispensable for BCR-ABL-mediated transformation. Exp Hematol. 2002;30:697–702. doi: 10.1016/S0301-472X(02)00808-1. PubMed DOI

Nawata R, Yujiri T, Nakamura Y, Ariyoshi K, Takahashi T, Sato Y, Oka Y, Tanizawa Y. MEK kinase 1 mediates the antiapoptotic effect of the Bcr-Abl oncogene through NF-kappaB activation. Oncogene. 2003;22:7774–7780. doi: 10.1038/sj.onc.1206901. PubMed DOI

Hakansson P, Lassen C, Olofsson T, Baldetorp B, Karlsson A, Gullberg U, Fioretos T. Establishment and phenotypic characterization of human U937 cells with inducible P210 BCR/ABL expression reveals upregulation of CEACAM1 (CD66a) Leukemia. 2004;18:538–547. doi: 10.1038/sj.leu.2403255. PubMed DOI

Cilloni D, Messa F, Gottardi E, et al. Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro incubation. Cancer. 2004;101:979–988. doi: 10.1002/cncr.20457. PubMed DOI

Hakansson P, Nilsson B, Andersson A, Lassen C, Gullberg U, Fioretos T. Gene expression analysis of BCR/ABL1-dependent transcriptional response reveals enrichment for genes involved in negative feedback regulation. Genes Chromosom Cancer. 2008;47:267–275. doi: 10.1002/gcc.20528. PubMed DOI

Bruennert D, Czibere A, Bruns I, Kronenwett R, Gattermann N, Haas R, Neumann F. Early in vivo changes of the transcriptome in Philadelphia chromosome-positive CD34+ cells from patients with chronic myelogenous leukaemia following imatinib therapy. Leukemia. 2009;23:983–985. doi: 10.1038/leu.2008.337. PubMed DOI

Bhattacharyya J, Mihara K, Yasunaga S, Tanaka H, Hoshi M, Takihara Y, Kimura A. BMI-1 expression is enhanced through transcriptional and posttranscriptional regulation during the progression of chronic myeloid leukemia. Ann Hematol. 2009;88:333–340. doi: 10.1007/s00277-008-0603-8. PubMed DOI

Graham SM, Vass JK, Holyoake TL, Graham GJ. Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources. Stem Cells. 2007;25:3111–3120. doi: 10.1634/stemcells.2007-0250. PubMed DOI

Bruns I, Czibere A, Fischer JC, et al. The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence. Leukemia. 2009;23:892–899. doi: 10.1038/leu.2008.392. PubMed DOI

Hughes TR, Mao M, Jones AR, et al. Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nat Biotechnol. 2001;19:342–347. PubMed

Greiner J, Ringhoffer M, Taniguchi M, Li L, Schmitt A, Shiku H, Dohner H, Schmitt M. mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies. Int J Cancer. 2004;108:704–711. doi: 10.1002/ijc.11623. PubMed DOI

Elisseeva OA, Oka Y, Tsuboi A, et al. Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies. Blood. 2002;99:3272–3279. doi: 10.1182/blood.V99.9.3272. PubMed DOI

Yamagami T, Sugiyama H, Inoue K, et al. Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides: implications for the involvement of WT1 in leukemogenesis. Blood. 1996;87:2878–2884. PubMed

Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE, Davis MM. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med. 2000;6:1018–1023. doi: 10.1038/79526. PubMed DOI

Bories D, Raynal MC, Solomon DH, Darzynkiewicz Z, Cayre YE. Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells. Cell. 1989;59:959–968. doi: 10.1016/0092-8674(89)90752-6. PubMed DOI

Roman-Gomez J, Jimenez-Velasco A, Agirre X, et al. Epigenetic regulation of PRAME gene in chronic myeloid leukemia. Leuk Res. 2007;31:1521–1528. doi: 10.1016/j.leukres.2007.02.016. PubMed DOI

Rezvani K, Yong AS, Tawab A, et al. Ex vivo characterization of polyclonal memory CD8+ T-cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia. Blood. 2009;113:2245–2255. doi: 10.1182/blood-2008-03-144071. PubMed DOI PMC

Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005;122:835–847. doi: 10.1016/j.cell.2005.07.003. PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...