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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林凱信 | |
dc.contributor.author | Meng-Ju Li | en |
dc.contributor.author | 李孟如 | zh_TW |
dc.date.accessioned | 2021-06-13T15:27:29Z | - |
dc.date.available | 2016-10-07 | |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-10 | |
dc.identifier.citation | 1. Chen J, Odenike O, Rowley JD, Chen J, Odenike O, Rowley JD: Leukaemogenesis: more than mutant genes. Nature Reviews Cancer 2010, 10(1):23-36.
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Dohner H: Implication of the molecular characterization of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2007:412-419. 7. Langemeijer SM, Aslanyan MG, Jansen JH: TET proteins in malignant hematopoiesis. Cell Cycle 2009, 8(24):4044-4048. 8. Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R et al: Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood 2009, 114(1):144-147. 9. Bacher U, Haferlach C, Schnittger S, Kohlmann A, Kern W, Haferlach T: Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies. Ann Hematol 2010, 89(7):643-652. 10. Mullighan CG, Mullighan CG: TET2 mutations in myelodysplasia and myeloid malignancies. Nature Genetics 2009, 41(7):766-767. 11. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens-Linders E, van Hoogen P, van Kessel AG, Raymakers RA et al: Acquired mutations in TET2 are common in myelodysplastic syndromes. Nature Genetics 2009, 41(7):838-842. 12. Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y: Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 2010, 466(7310):1129-1133. 13. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Mass, x00E, Kosmider O, Le Couedic JP, Robert F et al: Mutation in TET2 in myeloid cancers. New England Journal of Medicine 2009, 360(22):2289-2301. 14. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L et al: Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009, 324(5929):930-935. 15. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF et al: Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010, 18(6):553-567. 16. Mohr F, Dohner K, Buske C, Rawat VP: TET Genes: new players in DNA demethylation and important determinants for stemness. Exp Hematol 2011. 17. Ho PA, Kutny MA, Alonzo TA, Gerbing RB, Joaquin J, Raimondi SC, Gamis AS, Meshinchi S: Leukemic mutations in the methylation-associated genes DNMT3A and IDH2 are rare events in pediatric AML: A report from the Children's Oncology Group. Pediatr Blood Cancer 2011, 57(2):204-209. 18. Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, O'Keefe CL, Ganetzky R, McDevitt MA, Maciejewski JP et al: Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood 2009, 113(25):6403-6410. 19. Mohamedali AM, Smith AE, Gaken J, Lea NC, Mian SA, Westwood NB, Strupp C, Gattermann N, Germing U, Mufti GJ et al: Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. Journal of Clinical Oncology 2009, 27(24):4002-4006. 20. Bacher U, Schnittger S, Haferlach T: Molecular genetics in acute myeloid leukemia. Curr Opin Oncol 2010, 22(6):646-655. 21. Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, An J, Lamperti ED, Koh KP, Ganetzky R et al: Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 2010. 22. Bacher U, Haferlach C, Schnittger S, Kohlmann A, Kern W, Haferlach T: Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies. Ann Hematol. 23. Nibourel O, Kosmider O, Cheok M, Boissel N, Renneville A, Philippe N, Dombret H, Dreyfus F, Quesnel B, Geffroy S et al: Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood, 116(7):1132-1135. 24. Smith AE, Mohamedali AM, Kulasekararaj A, Lim Z, Gaken J, Lea NC, Przychodzen B, Mian SA, Nasser EE, Shooter C et al: Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood 2010, 116(19):3923-3932. 25. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D et al: Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC Cancer, 10:401. 26. Langemeijer SM, Jansen JH, Hooijer J, van Hoogen P, Stevens-Linders E, Massop M, Waanders E, van Reijmersdal SV, Stevens-Kroef MJ, Zwaan CM et al: TET2 mutations in childhood leukemia. Leukemia 2011, 25(1):189-192. 27. Radtke I, Mullighan CG, Ishii M, Su X, Cheng J, Ma J, Ganti R, Cai Z, Goorha S, Pounds SB et al: Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America 2009, 106(31):12944-12949. 28. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA et al: Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010, 115(3):453-474. 29. Bernasconi P, Bernasconi P: Molecular pathways in myelodysplastic syndromes and acute myeloid leukemia: relationships and distinctions-a review. British Journal of Haematology 2008, 142(5):695-708. 30. Hellstrom-Lindberg E: Significance of JAK2 and TET2 mutations in myelodysplastic syndromes. Blood Rev 2010, 24(2):83-90. 31. Saint-Martin C, Leroy G, Delhommeau F, Panelatti G, Dupont S, James C, Plo I, Bordessoule D, Chomienne C, Delannoy A et al: Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms. Blood 2009, 114(8):1628-1632. 32. Schaub FX, Looser R, Li S, Hao-Shen H, Lehmann T, Tichelli A, Skoda RC, Schaub FX, Looser R, Li S et al: Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood 2010, 115(10):2003-2007. 33. Couronne L, Lippert E, Andrieux J, Kosmider O, Radford-Weiss I, Penther D, Dastugue N, Mugneret F, Lafage M, Gachard N et al: Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias. Leukemia 2010, 24(1):201-203. 34. Kosmider O, Gelsi-Boyer V, Ciudad M, Racoeur C, Jooste V, Vey N, Quesnel B, Fenaux P, Bastie JN, Beyne-Rauzy O et al: TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica 2009, 94(12):1676-1681. 35. Mallo M, Osca G, Solorzano J, Arenillas L, Florensa L, Sole F: TET2 gene is not deleted in chronic myelomonocytic leukemia: a FISH retrospective study. Haematologica 2010, 95(10):1798-1800. 36. Nibourel O, Kosmider O, Cheok M, Boissel N, Renneville A, Philippe N, Dombret H, Dreyfus F, Quesnel B, Geffroy S et al: Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood 2010, 116(7):1132-1135. 37. Metzeler KH, Maharry K, Radmacher MD, Mrozek K, Margeson D, Becker H, Curfman J, Holland KB, Schwind S, Whitman SP et al: TET2 Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. J Clin Oncol 2011. 38. Kohlmann A, Grossmann V, Klein HU, Schindela S, Weiss T, Kazak B, Dicker F, Schnittger S, Dugas M, Kern W et al: Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol 2010, 28(24):3858-3865. 39. Kosmider O, Gelsi-Boyer V, Cheok M, Grabar S, Della-Valle V, Picard F, Viguie F, Quesnel B, Beyne-Rauzy O, Solary E et al: TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood 2009, 114(15):3285-3291. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37418 | - |
dc.description.abstract | 背景及目的:兒童急性骨髓性白血病(acute myeloid leukemia, AML)佔兒童白血病的10%。隨著診斷及治療技術的進步,近年來成績已大幅進步,根據台灣兒童癌症基金會報告,五年無事件存活率(event free survival,EFS)為32%~54%及五年總存活率(overall survival,OS)為36%~66%。然而仍舊有高達三成的病人會產生復發,治療成績尚有進步空間且致病機轉仍不完全清楚。TET2(tet oncogene family member)為造血機制調節及腫瘤抑制基因,近年來其突變好發於成人急性骨髓性白血病且與預後相關,唯於兒童急性骨髓性白血病仍少有報導。本研究欲探討兒童急性骨髓性白血病患者TET2基因變異情況,分析與臨床表現及與預後相關性。
方法:本研究分析自1997年1月至2010年7月期間至台大醫院就醫56位急性骨髓性白血病病童,取其診斷時骨髓檢體,建立PCR檢測TET2基因流程並定序。於兒童癌症基金會收集臨床表現,以卡方檢定、t檢定、Kaplan-Meier存活分析法及迴歸分析探討TET2基因變異情況與臨床表現及預後相關性。 結果:本研究共分析56位病人,男女數目為34/22 (60.7%/39.3%)。平均年齡為9.07 ± 5.4(0.01~17.54)歲,發病時的白血球數目平均為86±103(1-392)k/uL。其中42.9%病患復發(N=24),55.4%病患死亡(N=31)。其中44人(78.6%)有TET2單一核苷酸多形性,只有一個位點(A1865G)是位於高保留區。分析TET2基因多形性與臨床表現及預後,發現並無相關。使用生物資訊學分析未報告過的點突變,其中3個單一核苷酸多形性經3個生物資訊軟體同時判定為「可能具致病性」,分析與臨床表現及預後並無相關。 結論:TET2基因突變於兒童骨髓性白血病的盛行率遠較成人低,且其基因多形性與臨床表現、無事件存活時間和整體存活時間皆無相關。 | zh_TW |
dc.description.abstract | Background and Purpose. Acute myeloid leukemia (AML) accounts for 10% of childhood leukemia. The tet oncogene family member 2 (TET2) gene mutations are found in adult AML and is associated to prognosis. However, the report in childhood AML is limited. Here, we assess the prevalence of TET2 polymorphism in childhood AML and to identify its association with prognosis.
Method. We collected pediatric patients in national Taiwan university hospital from January 1997 to June 2010. DNA was isolated from bone marrow cells at diagnosis and sequence analysis was carried out for TET2 gene. Chi-square, t-test, Kaplan-Meier survival method and regression analysis are used for testing the association of TET2 polymorphisms with clinical presentation and prognosis. Result. Total of 56 pediatric AML patients were enrolled. The mean age is 9.07 ± 5.4 (0.01~17.54) years. There are 34 (60.7%) males. Twenty-four (42.9%) patients had relapse and the overall survival rate is 45%. The prevalence of TET2 polymorphism is 78.6% (44/56). There was no association between TET2 polymorphism to clinical presentation or prognosis. Conclusions. The prevalence of TET2 mutation in pediatric AML patients is far lower than in adults and is not associated with clinical presentation or prognosis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:27:29Z (GMT). No. of bitstreams: 1 ntu-100-P98421015-1.pdf: 1442965 bytes, checksum: 24330336f2b0f2bc5e21381c9fa4e63c (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 目 錄
口試委員會審定書……………………..…………………………… i 誌謝…………………………………………………………………. ii 中文摘要…………………………………………………………... iii Abstract…………………………………………………………... iv 碩士論文內容 第一章、緒論…………………………………………………………. 1 第一節、背景……………………………………………...………… 1 第二節、文獻回顧…………….…………………………………….. 1 第三節、欲研究的問題及其重要性….…..………………………… 5 第四節、研究的假說與特定目的………………………………….… 5 第二章、研究方法與材料……………………………………………. 7 第一節、病人、檢體及治療.…………………………………… 7 第二節、檢體處理及序列分析…….…………………………… 7 第三節、治療…………………………………………………… 10 第四節、統計分析……………………………………………… 10 第三章、結果………………………………………………………… 12 第一節、基本資料……………………………………………… 12 第二節、TET2基因多形性表現………………………………… 12 第三節、臨床表現與死亡與否的相關性……………………… 13 第四節、臨床表現與復發與否的相關性……………………… 13 第五節、臨床表現與有無TET2單一核苷酸多形性的相關…. 13 第六節、臨床表現對死亡之迴歸分析………………………… 13 第七節、臨床表現對復發之迴歸分析………………………… 14 第八節、TET2基因多形性表現與預後相關…………………… 15 第九節、藉由生物資訊學探討TET2基因多形性表現與預後相關...................................................... 15 第四章、討論………………………………………………………… 16 第一節、兒童急性骨髓性白血病TET2基因突變情形………… 16 第二節、兒童急性骨髓性白血病TET2基因多形性與預後的相關…….................................................. 16 第三節、生物資訊學於TET2基因多形性的應用……………… 17 第四節、本研究的限制………………………………………… 18 第五章、展望………………………………………………………… 20 英文簡要Summary…………………………………………………… 21 參考文獻……………………………………………………………… 37 圖……………………………………………………………………… 41 表……………………………………………………………………… 51 | |
dc.language.iso | zh-TW | |
dc.title | TET2基因變異於兒童急性骨髓性白血病之盛行率及預後相關 | zh_TW |
dc.title | Prevalence & prognosis value of TET2 gene polymorphisms in childhood acute myeloid leukemia | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 高嘉宏,田蕙芬 | |
dc.subject.keyword | 兒童急性骨髓性白血病,TET2基因,基因多形性,單一核苷,酸多形性, | zh_TW |
dc.subject.keyword | Acute myeloid leukemia,Pediatric,TET2,Single nucleotide polymorphism, | en |
dc.relation.page | 76 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-11 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
顯示於系所單位: | 臨床醫學研究所 |
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