Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 12/2011

01.12.2011 | Original Paper

Identification of GLIPR1 tumor suppressor as methylation-silenced gene in acute myeloid leukemia by microarray analysis

verfasst von: Yan-Hua Xiao, Xin-Hui Li, Tan Tan, Ting Liang, Hong Yi, Mao-Yu Li, Gu-Qing Zeng, Xun-Xun Wan, Jia-Quan Qu, Qiu-Yan He, Jian-Huang Li, Yu Chen, Zhi-Qiang Xiao

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To identify methylation-silenced genes in acute myeloid leukemia (AML).

Methods

Microarray analyses were performed in AML cell line HL-60 cells exposed to the demethylating agent 5-aza-2dC. The methylation status and expression of glioma pathogenesis-related protein 1 (GLIPR1), one of highly induced genes by demethylation, were further detected in six hematopoietic malignancy cell lines and 260 bone marrow samples from leukemia patients and nonmalignant diseases as control, as well as pre-treated and post-treated bone marrow samples from 24 complete remission AML patients received chemotherapy using MS-PCR, bisulfite DNA sequencing, RT-PCR, and Western blotting.

Results

One hundred and nine genes were significantly induced by demethylation in HL-60 cells, 12 genes of which were confirmed by RT-PCR. GLIPR1, a tumor suppressor gene, was frequently methylation-silenced in AML cell lines and AML patients, but not in the other hematopoietic malignancy cell lines and patients. The frequencies of methylation-silenced GLIPR1 in the pre-treatment were significantly higher than those in the post-treatment in complete remission AML patients.

Conclusion

We identify 109 genes induced by demethylation in HL-60 cells, and demonstrate that GLIPR1 is a methylation-silenced gene in the AML patients, and may serve as a marker for monitoring disease activity during therapy in the AML patients. The data provide the important information for studying the pathogenesis of AML and discovering the target genes of methylating agents.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Agrawal S, Hofmann WK, Tidow N, Ehrich M, van den Boom D, Koschmieder S et al (2007) The C/EBP{delta} tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood 109:3895–3905PubMedCrossRef Agrawal S, Hofmann WK, Tidow N, Ehrich M, van den Boom D, Koschmieder S et al (2007) The C/EBP{delta} tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood 109:3895–3905PubMedCrossRef
Zurück zum Zitat Chim CS, Liang R, Kwong YL (2002) Hypermethylation of gene promoters in hematological neoplasia. Hematol Oncol 20:167–176PubMedCrossRef Chim CS, Liang R, Kwong YL (2002) Hypermethylation of gene promoters in hematological neoplasia. Hematol Oncol 20:167–176PubMedCrossRef
Zurück zum Zitat Claus R, Almstedt M, Lübbert M (2005) Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents. Semin Oncol 32:511–520PubMedCrossRef Claus R, Almstedt M, Lübbert M (2005) Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents. Semin Oncol 32:511–520PubMedCrossRef
Zurück zum Zitat Gingras MC, Margolin JF (2000) Differential expression of multiple unexpected genes during U937 cell and macrophage differentiation detected by suppressive subtractive hybridization. Exp Hematol 28:65–76PubMedCrossRef Gingras MC, Margolin JF (2000) Differential expression of multiple unexpected genes during U937 cell and macrophage differentiation detected by suppressive subtractive hybridization. Exp Hematol 28:65–76PubMedCrossRef
Zurück zum Zitat Griffiths EA, Gore SD (2008) DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes. Semin Hematol 45:23–30PubMedCrossRef Griffiths EA, Gore SD (2008) DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes. Semin Hematol 45:23–30PubMedCrossRef
Zurück zum Zitat Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054PubMedCrossRef Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054PubMedCrossRef
Zurück zum Zitat Herman JG, Civin CI, Issa JP, Collector MI, Sharkis SJ, Baylin SB (1997) Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. Cancer Res 57:837–841PubMed Herman JG, Civin CI, Issa JP, Collector MI, Sharkis SJ, Baylin SB (1997) Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. Cancer Res 57:837–841PubMed
Zurück zum Zitat Issa JP, Baylin SB, Herman JG (1997) DNA methylation changes in hematologic malignancies: biologic and clinical implications. Leukemia 11:S7–S11PubMed Issa JP, Baylin SB, Herman JG (1997) DNA methylation changes in hematologic malignancies: biologic and clinical implications. Leukemia 11:S7–S11PubMed
Zurück zum Zitat Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S et al (2004) Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103:1635–1640PubMedCrossRef Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S et al (2004) Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103:1635–1640PubMedCrossRef
Zurück zum Zitat Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20:85–93PubMedCrossRef Jones PA, Taylor SM (1980) Cellular differentiation, cytidine analogs and DNA methylation. Cell 20:85–93PubMedCrossRef
Zurück zum Zitat Katzenellenbogen RA, Baylin SB, Herman JG (1999) Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood 93:4347–4353PubMed Katzenellenbogen RA, Baylin SB, Herman JG (1999) Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood 93:4347–4353PubMed
Zurück zum Zitat Li L, Abdel Fattah E, Cao G, Ren C, Yang G, Goltsov AA et al (2008) Glioma pathogenesis-related protein 1 exerts tumor suppressor activities through proapoptotic reactive oxygen species-c-Jun-NH2 kinase signaling. Cancer Res 68:434–443PubMedCrossRef Li L, Abdel Fattah E, Cao G, Ren C, Yang G, Goltsov AA et al (2008) Glioma pathogenesis-related protein 1 exerts tumor suppressor activities through proapoptotic reactive oxygen species-c-Jun-NH2 kinase signaling. Cancer Res 68:434–443PubMedCrossRef
Zurück zum Zitat Liang T, Tan T, Xiao Y, Yi H, Li C, Peng F et al (2009) Methylation and expression of glioma pathogenesis-related protein 1 gene in acute myeloid leukemia. Zhong Nan Da Xue Xue Bao Yi Xue Ban 34:388–394PubMed Liang T, Tan T, Xiao Y, Yi H, Li C, Peng F et al (2009) Methylation and expression of glioma pathogenesis-related protein 1 gene in acute myeloid leukemia. Zhong Nan Da Xue Xue Bao Yi Xue Ban 34:388–394PubMed
Zurück zum Zitat Melki JR, Vincent PC, Brown RD, Clark SJ (2000) Hypermethylation of E-cadherin in leukemia. Blood 95:3208–3213PubMed Melki JR, Vincent PC, Brown RD, Clark SJ (2000) Hypermethylation of E-cadherin in leukemia. Blood 95:3208–3213PubMed
Zurück zum Zitat Momparler RL (2005) Epigenetic therapy of cancer with 5-aza-2′-deoxycytidine (decitabine). Semin Oncol 32:443–451PubMedCrossRef Momparler RL (2005) Epigenetic therapy of cancer with 5-aza-2′-deoxycytidine (decitabine). Semin Oncol 32:443–451PubMedCrossRef
Zurück zum Zitat Murphy EV, Zhang Y, Zhu W, Biggs J (1995) The human glioma pathogenesis-related protein is structurally related to plant pathogenesis-related proteins and its gene is expressed specifically in brain tumors. Gene 159:131–135PubMedCrossRef Murphy EV, Zhang Y, Zhu W, Biggs J (1995) The human glioma pathogenesis-related protein is structurally related to plant pathogenesis-related proteins and its gene is expressed specifically in brain tumors. Gene 159:131–135PubMedCrossRef
Zurück zum Zitat Naruishi K, Timme TL, Kusaka N, Fujita T, Yang G, Goltsov A et al (2006) Adenoviral vector-mediated RTVP-1 gene-modified tumor cell based vaccine suppresses the development of experimental prostate cancer. Cancer Gene Ther 13:658–663PubMedCrossRef Naruishi K, Timme TL, Kusaka N, Fujita T, Yang G, Goltsov A et al (2006) Adenoviral vector-mediated RTVP-1 gene-modified tumor cell based vaccine suppresses the development of experimental prostate cancer. Cancer Gene Ther 13:658–663PubMedCrossRef
Zurück zum Zitat Ng MH, Chung YF, Lo KW, Wickham NW, Lee JC, Huang DP (1997) Frequent hypermethylation of p16 and p15 genes in multiple myeloma. Blood 89:2500–2506PubMed Ng MH, Chung YF, Lo KW, Wickham NW, Lee JC, Huang DP (1997) Frequent hypermethylation of p16 and p15 genes in multiple myeloma. Blood 89:2500–2506PubMed
Zurück zum Zitat Plimack ER, Kantarjian HM, Issa JP (2007) Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma 48:1472–1481PubMedCrossRef Plimack ER, Kantarjian HM, Issa JP (2007) Decitabine and its role in the treatment of hematopoietic malignancies. Leuk Lymphoma 48:1472–1481PubMedCrossRef
Zurück zum Zitat Ren C, Ren CH, Li L, Goltsov AA, Thompson TC (2002) mRTVP-1, a novel p53 target gene with proapoptotic activities. Mol Cell Biol 22:3345–3357PubMedCrossRef Ren C, Ren CH, Li L, Goltsov AA, Thompson TC (2002) mRTVP-1, a novel p53 target gene with proapoptotic activities. Mol Cell Biol 22:3345–3357PubMedCrossRef
Zurück zum Zitat Ren C, Li L, Yang G, Timme TL, Goltsov A, Ren C et al (2004) RTVP-1, a tumor suppressor inactivated by methylation in prostate cancer. Cancer Res 64:969–976PubMedCrossRef Ren C, Li L, Yang G, Timme TL, Goltsov A, Ren C et al (2004) RTVP-1, a tumor suppressor inactivated by methylation in prostate cancer. Cancer Res 64:969–976PubMedCrossRef
Zurück zum Zitat Rich T, Chen P, Furman F, Huynh N, Israel MA (1996) RTVP-1, a novel human gene with sequence similarity to genes of diverse species, is expressed in tumor cell lines of glial but not neuronal origin. Gene 180:125–130PubMedCrossRef Rich T, Chen P, Furman F, Huynh N, Israel MA (1996) RTVP-1, a novel human gene with sequence similarity to genes of diverse species, is expressed in tumor cell lines of glial but not neuronal origin. Gene 180:125–130PubMedCrossRef
Zurück zum Zitat Rüter B, Wijermans PW, Lübbert M (2004) DNA methylation as a therapeutic target in hematologic disorders: recent results in older patients with myelodysplasia and acute myeloid leukemia. Int J Hematol 80:128–135PubMedCrossRef Rüter B, Wijermans PW, Lübbert M (2004) DNA methylation as a therapeutic target in hematologic disorders: recent results in older patients with myelodysplasia and acute myeloid leukemia. Int J Hematol 80:128–135PubMedCrossRef
Zurück zum Zitat Satoh T, Timme TL, Saika T, Ebara S, Yang G, Wang J et al (2003) Adenoviral vector mediated mRTVP-1 gene therapy for prostate cancer. Hum Gene Ther 14:91–101PubMedCrossRef Satoh T, Timme TL, Saika T, Ebara S, Yang G, Wang J et al (2003) Adenoviral vector mediated mRTVP-1 gene therapy for prostate cancer. Hum Gene Ther 14:91–101PubMedCrossRef
Zurück zum Zitat Szyperski T, Fernandez C, Mumenthaler C, Wuthrich K (1998) Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system. Proc Natl Acad Sci USA 95:2262–2266PubMedCrossRef Szyperski T, Fernandez C, Mumenthaler C, Wuthrich K (1998) Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system. Proc Natl Acad Sci USA 95:2262–2266PubMedCrossRef
Zurück zum Zitat Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL, Issa JP (2001) Methylation profiling in acute myeloid leukemia. Blood 97:2823–2829PubMedCrossRef Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL, Issa JP (2001) Methylation profiling in acute myeloid leukemia. Blood 97:2823–2829PubMedCrossRef
Zurück zum Zitat Weller M, Malipiero U, Aguzzi A, Reed JC, Fontana A (1995) Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J Clin Invest 95:2633–2643PubMedCrossRef Weller M, Malipiero U, Aguzzi A, Reed JC, Fontana A (1995) Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J Clin Invest 95:2633–2643PubMedCrossRef
Metadaten
Titel
Identification of GLIPR1 tumor suppressor as methylation-silenced gene in acute myeloid leukemia by microarray analysis
verfasst von
Yan-Hua Xiao
Xin-Hui Li
Tan Tan
Ting Liang
Hong Yi
Mao-Yu Li
Gu-Qing Zeng
Xun-Xun Wan
Jia-Quan Qu
Qiu-Yan He
Jian-Huang Li
Yu Chen
Zhi-Qiang Xiao
Publikationsdatum
01.12.2011
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2011
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-011-1065-2

Weitere Artikel der Ausgabe 12/2011

Journal of Cancer Research and Clinical Oncology 12/2011 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.