Стандартизированное исследование экспрессии генов BCR-ABL, PRAME и WT1 у больных хроническим миелолейкозом
Диссертация
Частота гиперэкспрессии генов PRAME и WT1 не отличается у больных ХМЛ в ХФ и 2-й ХФ. Можно заключить, что в фазе акселерации не происходит необратимого изменения экспрессии этих генов, отражающего вовлечение дополнительных метаболических путей клетки. При уменьшении опухолевой нагрузки у больных ХМЛ при терапии иматинибом не происходит значимого изменения частоты гиперэкспрессии гена PRAME, при… Читать ещё >
Содержание
- Список сокращений
- Глава 1. Обзор литературы
- 1. 1. Структура и функции гена BCR-ABL, метаболические пути, участвующие в патогенезе XMJI. Взаимосвязь структуры химерного онкогена BCR-ABL с фенотипом заболевания
- 1. 2. Молекулярно-генетические основы терапии ХМЛ ингибиторами тирозинкиназ
- 1. 3. Факторы прогрессии заболевания
- 1. 4. Молекулярный мониторинг экспрессии BCR-ABL у больных ХМЛ: характеристика метода, его оптимизация и стандартизация
- 1. 5. Роль молекулярного мониторинга при терапии ХМЛ ингибиторами тирозинкиназ
- 1. 6. Онкомаркер PRAME — экспрессия при гемобластозах, иммунологическая роль, исследование функций белка в клетке
- 1. 7. Ген WT1 — строение, функции белка, экспрессия при гемобластозах
- Глава 2. Материалы и методы исследования
- Глава 3. Результаты собственных исследований и обсуждение
- 3. 1. Разработка тест-систем, определение характеристик метода ПЦР в реальном времени, стандартизация метода молекулярного мониторинга
- BCR-ABL
- 3. 2. Сопоставление данных молекулярного и цитогенетического анализа
- 3. 2. 1. Валидация метода молекулярной диагностики
- 3. 2. 2. Корреляция у больных с ПЦО уровня экспрессии BCR-ABL и стабильности цитогенетического ответа
- 3. 2. 3. Динамика молекулярного и цитогенетического ответов у больных с разным ответом на терапию
- 3. 3. Достижение молекулярного ответа у больных ХМЛ, начавших терапию иматинибом в ранней хронической фазе (РХФ) и в поздней хронической фазе (ПХФ)
- 3. 3. 1. Общее достижение БМО и ПМО в двух группах за весь период наблюдения
- 3. 3. 2. Динамика достижения молекулярного ответа в сроки 6месяцев терапии иматинибом
- 3. 3. 3. Динамика первичного достижения молекулярного ответа за 1годы терапии иматинибом
- 3. 4. Взаимосвязь уровня экспрессии BCR-ABL у больных ХФ ХМЛ на ранних сроках терапии и достижения молекулярного и цитогенетического ответа на терапии иматинибом
- 3. 5. Экспрессия генов PRAME и WT1 у больных ХМЛ
- 3. 5. 1. Частота встречаемости и уровень экспрессии генов PRAME и WT1 у больных ХФ ХМЛ на разных сроках терапии иматинибом и у больных во 2-й ХФ
- 3. 5. 2. Соотношение уровней’экспрессии генов BCR-ABL, PRAME и WT у больных ХФ ХМЛ на терапии иматинибом
- 3. 5. 3. Зависимость последующего ответа на терапию иматинибом от уровня экспрессии генов PRAME и WT1 у больных ХФ ХМЛ
- 3. 5. 4. Экспрессия генов PRAME и WT1 у больных ХФ ХМ, резистентных к терапии иматинибом и больных с оптимальным ответом на терапию. Корреляция с мутационным статусом гена BCR-ABL
- 3. 2. Сопоставление данных молекулярного и цитогенетического анализа
Список литературы
- Melo JV, Deininger MWN. Biology of chronic myelogenous leukemia- signaling pathways of initiation and transformation. Hematol Oncol Clin North Am 2004- 18:545−68.
- Cilloni D., Saglio G. CML: a model for targeted therapy. Best Practice
- Research Clinical Haematology 2009- 22: 285−294
- Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci U S A 2006−103:2794−9.
- Epping MT, Bernards R. A causal role for the human tumor antigen preferentially expressed antigen of melanoma in cancer. Cancer Res. 2006 Nov 15−66(22): 10 639−4
- Yang L, Han Y, Saiz FS, Minden MD. A tumor suppressor and oncogene: the WT1 story. Leukemia (2007) 21, 868−876
- Na IK, Kreuzer KA, Lupberger J, Dorken B, le Coutre P. Quantitative RT-PCR of Wilms tumor gene transcripts (WT1) for the molecular monitoring of patients with accelerated phase bcr/abl + CML. Leuk Res. 2005 Mar-29(3):343−5
- Goldman J, Melo J. Chronic Myeloid Leukemia advances in biology and new approach to treatment. N Engl J Med 2003- 349:1451−64
- Calabretta B, Perrotti D. The biology of CML blast crisis. Blood 2004- 103: 4010−22.
- Ломана Е.Г., Моторин Д. В., Романова Е. Г., Зарицкий А. Ю. Хронический миелолейкоз до и после применения иматиниба. Онкогематология. 2009. № 2. С. 4−16.
- Туркина А.Г., Круглов С. С., Дружкова Г. А., и др.
- Цитогенетический ответ-маркер эффективности терапии ингибитором bcr-abl тирозинкиназы (гливеком) у больных хроническим миелолейкозом. Терапевтический архив. 2005. Т. 77. № 7. С. 42−47.
- Kurzrock R, Kantarjian HM, Druker BJ, Talpaz M. Philadelphia Chromosome-Positive Leukemias: From Basic Mechanisms to Molecular Therapeutics. Annals of Internal Medicine 2003- 138: 819−831.
- Rosenberg N, Witte ON. The viral and cellular forms of the Abelson (abl) oncogene. Adv Virus Res. 1988- 35:39−81.
- Hantschel O, Superti-Furga G. Regulation of the с-Abl and BCR-ABL tyrosine kinases. Nat Rev Mol Cell Biol. 2004−5:33−44.
- Smith JM, Katz S, Mayer BJ. Activation of the Abl tyrosine kinase in vivo by Src homology 3 domains from the Src homology 2/Src homology 3 adaptor Nek. J Biol Chem. 1999- 274:27 956−27 962.
- Van Etten RA. Cycling, stressed-out and nervous: cellular functions of c-Abl. Trends Cell Biol. 1999−9:179−86
- Kharbanda S, Pandey P, Morris PL, Whang Y, Xu Y, Sawant S, et al.
- Functional role for the c-Abl tyrosine kinase in meiosis I. Oncogene. 1998- 16: 1773−7. •
- Miao YJ, Wang JY. Binding of A/T-rich DNA by three high mobility group-like domains in c-Abl tyrosine kinase. J Biol Chem. 1996- 271:22 823−30.
- Yuan ZM, Huang Y, Ishiko T, Kharbanda S, Weichselbaum R, Kufe D. Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase. Proc Natl Acad Sci USA. 1997- 94:1437−40
- Laurent E, Talpaz M, Wetzler M, Kurzrock R. Cytoplasmic and nuclear localization of the 130 and 160 kDa Bcr proteins. Leukemia. 2000−14:1892−7.
- Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nat Rev Cancer. 2005- 5:172−183
- Pendergast AM, Quilliam LA, Cripe LD, et al. В CR-ABL in due e d oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 1993- 75:175−85.
- McWhirter JR, Galasso DL, Wang JY. A coiled-coil oligomerization domain of Bcr is essential for the transforming function of BCR-ABL oncoproteins. Mol Cell Biol 1993- 13:7587−95
- Smith KM, Yacobi R, Van Etten RA. Auto inhibition of BCR-ABL through its SH3 domain. Mol Cell 2003- 12:27−37
- Хоффбранд В., Петит Дж. Атлас-справочник Гематология. Москва, «Практика», 2007
- Cortez D, Reuther GW, Pendergast AM. The BCR-ABL tyrosine kinase activates mitotic signaling pathways and stimulates Gl-to-S phase transition in hematopoietic cells. Oncogene 1997−15:2333−42
- Raitano AB, Halpem JR, Hambuch TM, et al. The BCR-ABL leukemia oncogene activates Jun kinase and requires Jun for transformation. Proc Natl Acad Sei U S A 1995−92:11 746−50.
- Ilaria Jr RL, Van Etten RA. P210 and PI90 (BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chem 1996- 271:31 704−10
- Carlesso N, Frank DA, Griffin JD. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J Exp Med 1996−183:811−20.
- Sawyers CL, CallahanW, Witte ON. Dominant negative MYC blocks transformation by AB1 oncogenes. Cell 1992- 70:901−10.
- Xie S, Lin H, Sun T, et al. Jak2 is involved in c-Myc induction by BCR-ABL. Oncogene 2002−17:713746.
- Skorski T, Bellacosa A, Nieborowska-Skorska M, et al. Transformation of hematopoietic cells by BCR/ABL requires activation of a PI—3k/Akt-dependent pathway. EMBO J 1997- 16:6151−61.
- Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKT blocks apoptosis. Cell 1997- 88:435−7.
- Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, et al. Suppression of c-Myc induced apoptosis by Ras signalling through PI 3-kinase and PKB. Nature 1997−385:544−8.
- Sattler M, Mohi MG, Pride YB, et al. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 2002−1:479−92
- Verfaillie CM, Hurley R, Zhao RC, Prosper F, Delforge M, Bhatia R. Pathophysiology of CML: do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone? J Lab Clin Med 1997- 129(6):584- 91
- Durig J, Testa NG, Lord BI, Kasper C, Chang J, Telford N, et al. Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1 alpha. Leukemia 1999−13(12):2012- 22.
- Lewis JM, Baskaran R, Taagepera S, Schwartz MA, Wang JY. Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport. Proc Natl Acad Sei USA 1996- 93(26):15 174−9.
- Pane F, Intrieri M, Quintarelli C, IzzoB, Muccioli GC, Salvatore F. BCR/ABL genes and leukemic phenotype: from molecular mechanisms to clinical correlations. Oncogene (2002) 21, 8652 8667
- Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood 1996- 88(7):2375−84.
- Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton SW, et al. Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation. Genomics 1995−27(1):67 -82.
- Barnes DJ, Melo JV. Cytogenetic and Molecular Genetic Aspects of Chronic Myeloid Leukaemia // Acta Haematol.-2002.-N108.-P180−202.
- Saglio G, Pane F, Gottardi E, Frigeri F, Buonaiuto MR, Guerrasio A, et al. Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are expressed by chronic myelogenous leukemia patients at diagnosis. Blood 1996- 87(3): 1075- 80.
- Lichty BD, Keating A, Callum J, Yee K, Croxford R, Corpus G, et al. Expression of p210 and pi90 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. BrJ Haematol 1998−103(3):711- 5
- Quintas-Cardama A, Cortes J. Molecular biology of BCR-ABLl-positive chronic myeloid leukemia. Blood 2009- 113: 1619−29
- Pane F, Frigeri F, Sindona M, Luciano L, Ferrara F, Cimino R, et al. Neutrophilic-chronic myeloid leukemia (CML-N): a distinct disease with a specific molecular marker (BCR/ABLwith C3/A2 junction). Blood 1996- 88(7):24101.
- Buchdunger E, Zimmermann J, Mett H, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidme derivative. Cancer Res 1996−56:100−4.
- Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005 Apr l-105(7):2640−53.
- Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther. 2000−295:139−145.
- Carroll M, Ohno-Jones S, Tamura S, et al. CGP 57 148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood. 1997−90: 4947−4952.
- Schindler T, Bommann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanism for STI-571 inhibition of Abelson tirosin kinase//Science.-2000.-Vol 289.-P 1938−1942.
- Dmker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia// N Engl J Med.- 2006.-N355.-P2408−2417.
- Круглов C.C., Туркина А. Г., Хорошко Н. Д., и др. Резистентность при терапии гливеком у больных хроническим миелолейкозом в фазе акселерации. Гематология и трансфузиология. 2007. Т. 52. № 2. С. 17−24.
- Quintas-Cardama А, MD, Kantarjian НМ, MD, Cortes JE. Mechanisms of Primary and Secondary Resistance to Imatinib in Chronic Myeloid Leukemia. Cancer Control. 2009- Vol. 16, No. 2:122−131
- Martinelli G, Soverini S, Rosti G, Cilloni D, Baccarani M. New tyrosine kinase inhibitors in chronic myeloid leukemia// Haematologica.- 2005.-N90.-P534−541
- Weisberg E, Manley PW, BreitensteinW, et al. Characterization of AMN107, a selective inhibitor of native and mutant BCR-ABL// Cancer Cell.-2005.-N7.-P129−141.
- Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet// J Clin Oncol.- 2009.- Vol27.-N35.-P6041−51.
- Hughes TP, Branford S. Monitoring disease response to tyrosine kinase inhibitor therapy in CML// Hematology Am Soc Hematol Educ Program.- 2009.-P477−87.
- Jorgensen HG, Allan EK, Jordanides NE, Mountford JC, Holyoake TL. Nilotinib exerts equipotent anti-proliferative effects to imatinib and does not induce apoptosis in CD34 CML cells// Blood.- 2007.-N109.-P4016−4019.
- Copland M, Hamilton A, Elrick LJ, et al. Dasatinib (BMS-354 825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction// Blood.- 2006.-N107.-P4532−4539.
- Konig H, Holtz M, Modi H, et al. Enhanced BCRABL kinase inhibition does not result in increased inhibition of downstream signaling pathways or increased growth suppression in CML progenitors// Leukemia.- 2008.-N22.-P748−755.
- Ilaria RL Jr. Pathobiology of lymphoid and myeloid blast crisis and management issues// Hematology Am Soc Hematol Educ Program. 2005:188−94
- Zheng С, Li L, Haak M, et al. Gene expression profiling of CD34+ cells identifies a molecular signature of chronic myeloid leukemia blast crisis. Leukemia 2006- 20:1028−34.
- Barnes DJ, Schultheis В, Adedeji S, Melo JV. Dose-dependent effects of BCR-ABL in cell line models of different stages of chronic myeloid leukemia. Oncogene. 2005−24:6432−6440.
- Cambier N, Chopra R, Strasser A, Metcalf D, Elefanty AG. BCR-ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose-dependent manner. Oncogene. 1998−16:335−348.
- Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol. 2002- 107:76−94.
- Туркина А.Г., Домрачева E.B., Воронцова A.B. и др. Трисомия 8-й хромосомы в ph-негативных клетках костного мозга у больных хроническим миелолейкозом при лечении ингибиторами bcr-abl тирозинкиназ. Терапевтический архив. 2009. № 7. С. 29−36.
- Quintas-Cardama А, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc. 2006- 81:973−988.
- Neviani P, Santhanam R, Trotta R, et al. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell. 2005- 8:355−368.
- Yong ASM, Melo JV. The impact of gene profiling in chronic myeloid leukaemia. Best Practice & Research Clinical Haematology 22 (2009) 181—190
- 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(7):657−67.
- Perrotti D, Cesi V, Trotta R, et al. BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2. Nat Genet 2002−30:48−58.
- Melo JV, Barnes DJ. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer. 2007−7:441−453.
- Koptyra M, Falinski R, Nowicki MO, et al. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood. 2006−108:319−327.
- Morgan GJ, Hughes T, Janssen JWG, et al. Polymerase chain reaction for detection of residual leukaemia. Lancet. 1989- 1:928−929.
- Hughes TP, Morgan GJ, Martiat P, Goldman JM. Detection of residual leukemia after bone marrow transplantation: role of PCR in predicting relapse. Blood. 1991−77:874−878.
- Cross NCP, Lin F, Chase A, Bungey J, Hughes TP, Goldman JM. Competitive PCR to estimate the number of BCR-ABL transcripts in chronicmyeloid leukemia patients after bone marrow transplantation. Blood.1993−82:1929−1936
- Hochhaus A, Lin F, Reiter A, et al. Quantification of residual disease in chronic myelogenous leukemia patients on interferon-alpha therapy by competitive polymerase chain reaction. Blood. 1996−87:1549−1555.
- Mensink E, van de Locht A. Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukemia patients using realtime quantitative RT-PCR. Br J Haematol. 1998- 102:768−774.
- Branford S, Hughes TP, Rudzki Z. Monitoring chronic myeloid leukaemia therapy by real-time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics. Br J Haematol. 1999−107:587−599.
- ПЦР «в реальном времени». Под общей ред. Д. В. Ребрикова. Москва, «Бином», 2009
- Cross NCP. Standardisation of molecular monitoring for chronic myeloid leukaemia. Best Practice & Research Clinical Haematology 22 (2009) 355−365
- Radich JP, Gehly G, Gooley T, et al. Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients. Blood. 1995- 85:2632−2638.
- Dazzi F, Szydlo R, Cross NCP, et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allografting for chronic myeloid leukemia. Blood. 2000−96:2712−2716.
- Zhang T, Grenier S, Nwachukwu B, et al. Inter-laboratory comparison of chronic myeloid leukemia minimal residual disease monitoring: summary and recommendations. J Mol Diagn 2007 Sep-9(4):421−30.
- Wang YL, Lee JW, Cesarman E, et al. Molecular monitoring of chronic myeloid leukemia: identification of the most suitable internal control gene for realtime quantification of BCR-ABL transcripts. J Molecular Diagnostics. 2006−8:231−239
- Rulcova J, Zmekova V, Zemanova Z, et al. The effect of total-ABL, GUS and B2M control genes on BCR-ABL monitoring by real-time RT-PCR. Leuk Res. 2007- 31(4):483—91.
- Branford S, Cross NCP, Hochhaus A, et al. Rationale for therecommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia. Leukemia 2006 Nov-20(ll): 1925−30.
- Marino JH, Cook P, Miller KS. Accurate and statistically verified quantification of relative mRNA abundances using SYBR Green I and real-time RT-PCR. J Immunol Methods 2003- 283: 291−306
- Bustin SA, Nolan T. Pitfalls of quantitative real-time reversetranscription polymerase chain reaction. J Biomol Tech 2004- 15: 155—166.
- Stock W, Yu D, Karrison T, Sher D, Stone RM, Larson RA, Bloomfield
- CD. Quantitative real-time RT-PCR monitoring of BCR-ABL in chronicmyelogenous leukemia shows lack of agreement in blood and bone marrowsamples. Int J Oncol. 2006 May-28(5):1099−10
- Muller MC, Saglio G, Lin F, et al. An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica 2007 Jul-92(7):970−3.
- Yamada MF, Fujiwara T, Ishikawa I, et al. Interlaboratory comparison of quantitative RT-PCR based detection for minimal residual disease in leukemias: a standardization approach in Japan. Tohoku J Exp Med 2008 Feb-214(2):97−104.
- Muller MC, Erben P, Saglio G, et al. Harmonization of BCR-ABL mRNA quantification using a uniform multifunctional control plasmid in 37 international laboratories. Leukemia. 2008 Jan-22(l):96−102
- Hughes TP, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev. 2006 Jan-20(l):29−41.
- 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 Oct 9−349(15): 1423−32.
- Baccarani M, Saglio G, Goldman J, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006 Sep 15- 108(6): 1809−20
- Muller MC, Cross NCP, Erben P, et al. Harmonization of molecular monitoring of CML in Europe. Leukemia. 2009 Nov-23(l 1): 1957−63
- Kantaijian H, Talpaz M, O’Brien S, et al. Survival benefit with imatinib mesylate versus interferon-a-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood. 2006−108:1835−1840.
- Зарицкий А.Ю., Ломана Э. Г., Виноградова О.Ю и др. Результаты многоцентрового исследования терапии гливеком больных хроническим миелолейкозом в хронической фазе. Гематология и трансфузиология. 2007.1. Т. 52. № 2. С. 13−17.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: chronic myelogenous leukemia, version 2.2008. Fort Washington, PA: National Comprehensive Cancer Network, 2007.
- Radich JP. How I monitor residual disease in chronic myeloid leukemia. Blood.- 2009.-Vol 114.-N16.-P 3376−3381
- Kantarjian HM, Cortes J, Guilhot F, Hochhaus A, Baccarani M, Lokey L. Diagnosis and management of chronic myeloid leukemia: a survey of American and European practice patterns. Cancer. 2007−109:1365−1375.
- Ross DM, Branford S, Moore S, Hughes TP. Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL. Leukemia. 2006- 20:664−670.
- Jabbour E, Cortes JE, Kantaijian HM. Molecular Monitoring in Chronic Myeloid Leukemia: response to Tyrosine Kinase Inhibitors and Prognostic Implications. Cancer. 2008−112(10):2112−8
- Kantaijian H, Talpaz M, O’Brien S, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004−103:2873−2878
- Cortes J, Giles F, O’Brien S, et al. Result of high-dose imatinib mesylate in patients with Philadelphia chromosomepositive chronic myeloid leukemia after failure of interferon-alpha. Blood. 2003−102:83−86.
- Rosti G, Martinelli G, Bassi S, et al. Molecular response to imatinib in late chronic-phase chronic myeloid leukemia. Blood. 2004−103:2284−2290.
- Merx K, Muller MC, Kreil S, et al. Early reduction of BCRABL mRNA transcript levels predicts cytogenetic responsein chronic phase CML patients treated with imatinib after failure of interferon alpha. Leukemia. 2002- 16:15 791 583.
- Wang L, Pearson K, Ferguson JE, Clark RE. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. BrJ Haematol. 2003−120:990−999.
- Paschka P, Muller MC, Merx K, et al. Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission. Leukemia. 2003−17:1687−1694.
- Cortes J, Talpaz M, O’Brien S, et al. Molecular responses in patientswith chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005- 11:3425−3432. '
- Press RD, Love Z, Tronnes AA, et al. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate treated patients with CML. Blood., 2006- 107:42 504 256.
- Marin D, Milojkovic D, Olavarria E, et al. European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood. 2008- 112:4437−4444.
- Palandri F, Iacobucci I, Soverini S, et al. Treatment of Philadelphiapositive chronic myeloid leukemia with imatinib: importance of a stable molecular response. Clin Cancer Res. 2009−15:1059−1063.
- Branford S, Rudzki Z, Parkinson I, et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations. Blood. 2004- 104:29 262 932.
- Wang L, Knight K, Lucas C, Clark RE. The role of serial BCR-ABL transcript monitoring in predicting the emergence of BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia. Haematologica. 2006- 91:235−239.
- Press R, Galderisi C, Yang R, et al: A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response. Clin Cancer Res 13:61 366 144, 2007
- Rousselot P, Huguet F, Rea D, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood. 2007- 109:58−60.
- Ross DDM, Grigg A, Schwarer A, et al. The majority of chronic myeloid leukemia patients who cease imatinib after achieving a sustained complete molecular response (CMR) remain in CMR, and any relapses occur early abstract. Blood. 2008- 112:1102.
- Kantarjian H, O’Brien S, Shan J, et al. Cytogenetic and molccular responses and outcome in chronic myelogenous leukemia: need for new response definitions? Cancer. 2008−112:837−845.
- Matsushita M, Ikeda H, Kizaki M, Okamoto S, Ogasawara M, Ikeda Y, Kawakami Y. Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol. 2001 Mar-l 12(4):916−26
- Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M. The tumorassociated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome. Clin Cancer Res 2004- 10:430 713.
- Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, et al. Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches. Blood 2006- 108:4109−17.
- Steinbach D, Hermann J, Viehmann S, Zintl F, Gruhn B. Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Cancer Genet Cytogenet 2002- 133: 118−23.
- Paydas S, Tanriverdi K, Yavuz S, Disel U, Baslamisli F, Burgut R. PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects. Am J Hematol 2005- 79:257−61.
- Matsushita M, Yamazaki R, Ikeda H, Kawakami Y. Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies. Leuk Lymphoma. 2003 Mar-44(3):439−44
- Qin Y, Zhu H, Jiang B, Li J, Lu X, Li L, Ruan G, Liu Y, Chen S, Huang X. Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease. Leuk Res. 2009 Mar-33(3):384−9
- 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 Sep 23−122(6):835−47
- Steinbach D, Pfaffendorf N, Wittig S, Gruhn B. PRAlVfE expression is not associated with down-regulation of retinoic acid signaling in primary acute myeloid leukemia. Cancer Genet Cytogenet. 2007 Aug-177(l):51−4
- Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Navarro G, Jose-Eneriz ES, Garate L, Cordeu L, Cervantes F, Prosper F, Heiniger A, Torres A. Epigenetic regulation of PRAMIE gene in chronic myeloid leukemia. Leuk Res.2007 Nov-31(ll):1521−8
- Schenk T, Stengel S, Goellner S, Steinbach D, Saluz HP. Hypomethylation of PRAME is responsible for its aberrant overexpression in human malignancies. Genes Chromosomes Cancer. 2007 Sep-46(9):796−804
- Ortmann CA, Eisele L, Nuckel H, Klein-Hitpass L, Fuhrer A, Duhrsen U, Zeschnigk M. Aberrant hypomethylation of the cancer-testis antigen PRAME correlates with PRAME expression in acute myeloid leukemia. Ann Hematol. 2008 0ct-87(10):809−18
- 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 Mar-31(3):365−9
- Menke AL, van der Eb AJ, Jochemsen AG. The Wilms' tumor 1 gene: oncogene or tumor suppressor gene? Int Rev Cytol 1998- 181: 151−212.
- Rivera MN, Haber DA. Wilms' tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer 2005- 5:699−712.
- Hohenstein P, Hastie ND. The many facets of the Wilms' tumour gene, WT1. Human Molecular Genetics, 2006, Vol. 15, Review Issue No. 2 R196-R201
- Dallosso AR, Hancock AL, Brown KW, Williams AC, Jackson S, Malik K. Genomic imprinting at the WT1 gene involves a novel coding transcript (AWT1) that shows deregulation in Wilms’tumours. Hum Mol Genet 2004- 13: 405415.
- Ladomeiy M, Sommerville J, Woolner S, Slight J, Hastie N.(2003) Expression in Xenopus oocytes shows that WT1 binds transcripts in vivo, with a central role for zinc finger one. J. Cell Sei., 116, 1539−1549
- Niksic M, Slight J, Sanford JR, Caceres JF, Hastie ND. (2004) The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum. Mol. Genet., 13, 463171.
- Little M, Wells C. A clinical overview of WT1 gene mutations. Hum Mutat 1997- 9: 209−225
- Smith SI, Down M, Boyd AW, Li CL. Expression of the Wilms' tumor suppressor gene, WT1, reduces the tumorigenicity of the leukemic cell line Ml in C. B-17 scid/scid mice. Cancer Res 2000−60: 808—814.
- Fraizer G, Leahy R, Priyadarshini S, Graham K, Delacerda J, Diaz M. Suppression of prostate tumor cell growth in vivo by WT1, the Wilms' tumor suppressor gene. Int J Oncol 2004- 24: 461−471.
- Morrison DJ, English MA, Licht JD. WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak. Cancer Res 2005- 65: 8174−8182.
- Baird PN, Simmons PJ. Expression of the Wilms' tumor gene (WT1) in normal hemopoiesis. Exp Hematol 1997- 25: 312−320.
- Chiusa L, Francia di Celle P, Campisi P, Ceretto C, Marmont F, Pich A. Prognostic value of quantitative analysis of WT1 gene transcripts in adult acute lymphoblastic leukemia. Haematologica 2006- 91: 270−271.
- Tamaki H, Ogawa H, Ohyashiki K, Ohyashiki JH, Iwama H, Inoue K et al. The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. Leukemia 1999- 13: 393−399.
- Menssen HD, Renkl HJ, Rodeck U, Maurer J, Notter M, Schwartz S et al. Presence of Wilms' tumor gene (WT1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia 1995- 9: 1060−1067.
- Inoue K, Ogawa H, Sonoda Y, Kimura T, Sakabe H, Oka Y et al. Aberrant overexpression of the Wilms tumor gene (WT1) in human leukemia. Blood 1997- 89: 1405−1412.
- Kletzel M, Olzewski M, Huang W, Chou PM. Utility of WT1 as a reliable tool for the detection of minimal disease in children with leukemia. Pediatr Dev Pathol 2002- 5: 269−275.
- Cilloni D, Saglio G. WT1 as a universal marker for minimal residual disease detection and quantification in myeloid leukemias and in myelodysplastic syndrome. Acta Haematol 2004- 112:79−84.
- Barragan E, Cervera J, Bolufer P, Ballester S, Martin G, Fernandez P et al. Prognostic implications of Wilms' tumor gene (WT1) expression in patients with de novo acute myeloid leukemia. Haematologica 2004- 89: 926−933.
- Cao XS, Gu WY, Chen ZX, Hu SY, He J, Cen JN Bone marrow WT1 gene expression and clinical significance in chronic myelogenous leukemia. [Article in Chinese] Zhonghua Nei Ke Za Zhi. 2007 Apr-46(4):277−9
- Cilloni D, Messa F, Gottardi E, Fava M, Amiga F, Defilippi I, Carturan
- Otahalova E, Ullmannova-Benson V, Klamova FI, Haskovec C. WT1 expression in peripheral leukocytes of patients with chronic myeloid leukemia serves for the prediction of Imatinib resistance. Neoplasma. 2009−56(5):393−7
- Svensson E, Vidovic K, Lassen C, Richter J, Olofsson T, Fioretos T, Gullberg U. Deregulation of the Wilms' tumour gene 1 protein (WT1) by
- BCR/ABL1 mediates resistance to imatinib in human leukaemia cells. Leukemia. 2007 Dec-21(12):2485−94
- Karakas T, Miething CC, Maurer U, Weidmann E, Ackermann H, Hoelzer D et al. The coexpression of the apoptosis-related genes bcl-2 and WT1 in predicting survival in adult acute myeloid leukemia. Leukemia 2002- 16: 846—854.
- Ito K, Oji Y, Tatsumi N, Shimizu S, Kanai Y, Nakazawa T et al. Antiapoptotic function of 11AA (+)WT1 (Wilms' tumor gene) isoforms on the intrinsic apoptosis pathway.- Oncogene 2006- 25:4217—4229.
- Svedberg H, Chylicki K, Baldetorp B, Rauscher III FJ, Gullberg U. Constitutive expression of the Wilms' tumor gene (WT1) in the leukemic cell line U937 blocks parts of the differentiation program. Oncogene 1998- 16: 925−932.
- Keilholz U, Menssen HD, Gaiger A Menke A, Oji Y, Oka Y, Scheibenbogen C, Stauss H, Thiel E, Sugiyama H. Wilms' tumour gene 1 (WT1) in human neoplasia. Leukemia. 2005 Aug- 19(8): 1318−23.
- Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr-162(l):156−9