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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Oncohematology</journal-id><journal-title-group><journal-title xml:lang="en">Oncohematology</journal-title><trans-title-group xml:lang="ru"><trans-title>Онкогематология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1818-8346</issn><issn publication-format="electronic">2413-4023</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">748</article-id><article-id pub-id-type="doi">10.17650/1818-8346-2008-0-4-17-25</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>HEMATOLOGIC MALIGNANCIES: TREATMENT, SUPPORTIVE CARE</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ГЕМОБЛАСТОЗЫ: ЛЕЧЕНИЕ, СОПРОВОДИТЕЛЬНАЯ ТЕРАПИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Molecular genetics monitoring of tyrosine kinase inhibitor therapy for chronic myeloid leukemia</article-title><trans-title-group xml:lang="ru"><trans-title>Молекулярно-генетический мониторинг терапии хронического миелолейкоза ингибиторами тирозинкиназ</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kutsev</surname><given-names>S. I.</given-names></name><name xml:lang="ru"><surname>Куцев</surname><given-names>С. И.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Rostov-on-Don</p></bio><bio xml:lang="ru"><p>Ростов-на-Дону</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Velchenko</surname><given-names>M. V.</given-names></name><name xml:lang="ru"><surname>Вельченко</surname><given-names>М. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Rostov-on-Don</p></bio><bio xml:lang="ru"><p>Ростов-на-Дону</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Zelzer</surname><given-names>A. N.</given-names></name><name xml:lang="ru"><surname>Зельцер</surname><given-names>А. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Rostov-on-Don</p></bio><bio xml:lang="ru"><p>Ростов-на-Дону</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Rostov State Medical University</institution></aff><aff><institution xml:lang="ru">ГОУ ВПО Ростовский государственный медицинский университет</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2008-11-25" publication-format="electronic"><day>25</day><month>11</month><year>2008</year></pub-date><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>17</fpage><lpage>25</lpage><history><date date-type="received" iso-8601-date="2022-11-25"><day>25</day><month>11</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2022-11-25"><day>25</day><month>11</month><year>2022</year></date></history><permissions><copyright-year>2008</copyright-year><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://oncohematology.abvpress.ru/ongm/article/view/748">https://oncohematology.abvpress.ru/ongm/article/view/748</self-uri><abstract xml:lang="en"><p>Therapy for Ph-positive chronic myeloid leukemia (CML) with the tyrosine kinase inhibitor imatinib results in achievement of high hematological and cytogenetic response rates. However, most patients with a complete cytogenetic response were found to have a minimal residual disease. Therefore the role of molecular monitoring during CML therapy has recently increased. Regular molecular monitoring allows to early diagnosis of relapse and improvement of treatment outcome as a result of therapeutic intervention. For the imatinib-treated patients therapy resistance or increased BCR-ABL gene expression is an indication for kinase domain mutations testing. Detection of the mutations causing imatinib resistance is required for therapy choice. Real-time polymerase chain reaction and DNA sequencing should become customary for CML monitoring.</p></abstract><trans-abstract xml:lang="ru"><p>Терапия Ph-позитивного хронического миелолейкоза (ХМЛ) игибитором тирозинкиназ иматинибом приводит к достижению гематологической и цитогенетической ремиссии с большой частотой. Однако у большинства пациентов с полным цитогенетическим ответом молекулярными методами обнаруживается минимальная остаточная болезнь. В связи с этим роль молекулярного мониторинга терапии ХМЛ в последние годы возросла. Регулярный молекулярный мониторинг позволяет рано выявить рецидив и, как следствие терапевтической интервенции, улучшить результаты лечения. Для пациентов с ХМЛ, получающих лечение иматинибом, резистентность к проводимой терапии или повышение уровня экспрессии гена BCR-ABL служат показанием для анализа мутаций киназного домена этого гена. Выявление мутаций, ставших причиной резистентности к иматинибу, необходимо для выбора тактики терапии. Молекулярные методы полимеразной цепной реакции в режиме реального времени и ДНК-секвенирования должны войти в практику мониторинга ХМЛ.</p></trans-abstract><kwd-group xml:lang="en"><kwd>chronic myeloid leukemia</kwd><kwd>BCR-ABL gene expression</kwd><kwd>mutations of BCR-ABL gene kinase domain</kwd><kwd>tyrosine kinase inhibitors</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>хронический миелолейкоз</kwd><kwd>экспрессия гена BCR-ABL</kwd><kwd>мутации киназного домена гена BCR-ABL</kwd><kwd>ингибиторы тирозинкиназ</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">1. O’Brien S.G., Guilhot F., Larson R.A. 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.</mixed-citation><mixed-citation xml:lang="ru">O’Brien S.G., Guilhot F., Larson R.A. 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.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">2. Hehlmann R., Hochhaus A., Baccarani M. Chronic myeloid leukaemia. Lancet 2007;370:342—50.</mixed-citation><mixed-citation xml:lang="ru">Hehlmann R., Hochhaus A., Baccarani M. Chronic myeloid leukaemia. Lancet 2007;370:342—50.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">3. Jabbour E., Cortes J.E., Giles F.J. et al. Current and emerging treatment options in chronic myeloid leukemia. Cancer 2007;109:2171—81.</mixed-citation><mixed-citation xml:lang="ru">Jabbour E., Cortes J.E., Giles F.J. et al. Current and emerging treatment options in chronic myeloid leukemia. Cancer 2007;109:2171—81.</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">4. Goldman J.M. How I treat chronic myeloid leukemia in the imatinib era. Blood 2007;110:2828—37.</mixed-citation><mixed-citation xml:lang="ru">Goldman J.M. How I treat chronic myeloid leukemia in the imatinib era. Blood 2007;110:2828—37.</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">5. Gratwohl A., Brand R., Apperley J. et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, longterm data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 2006;91:513—21.</mixed-citation><mixed-citation xml:lang="ru">Gratwohl A., Brand R., Apperley J. et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, longterm data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 2006;91:513—21.</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">6. Baccarani M., Russo D., Rosti G. et al. Interferon-α for chronic myeloid leukemia. Semin Hematol 2003;40:22—33.</mixed-citation><mixed-citation xml:lang="ru">Baccarani M., Russo D., Rosti G. et al. Interferon-α for chronic myeloid leukemia. Semin Hematol 2003;40:22—33.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">7. Baccarani M., Martinelli G., Rosti G. et al. Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia. Blood 2004;104:4245—51.</mixed-citation><mixed-citation xml:lang="ru">Baccarani M., Martinelli G., Rosti G. et al. Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia. Blood 2004;104:4245—51.</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">8. Зарицкий А.Ю., Ломаиа Э.Г. Перспективы фармакотерапии ХМЛ. Эффект фармакотер 2006;1:38—42.</mixed-citation><mixed-citation xml:lang="ru">Зарицкий А.Ю., Ломаиа Э.Г. Перспективы фармакотерапии ХМЛ. Эффект фармакотер 2006;1:38—42.</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">9. 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 Leukemia Net. Blood 2006;108:1809—20.</mixed-citation><mixed-citation xml:lang="ru">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 Leukemia Net. Blood 2006;108:1809—20.</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">10. Туркина А.Г., Челышева Е.Ю. Цитогенетический и молекулярный ответ — ранние маркеры эффективности терапии Гливеком больных Ph+-хроническим миелолейкозом. Фарматека 2004;18(95).</mixed-citation><mixed-citation xml:lang="ru">Туркина А.Г., Челышева Е.Ю. Цитогенетический и молекулярный ответ — ранние маркеры эффективности терапии Гливеком больных Ph+-хроническим миелолейкозом. Фарматека 2004;18(95).</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">11. Мисюрин А.В., Аксенова Е.В., Крутов А.А. и др. Молекулярная диагностика хронического миелолейкоза. Гематол трансфузиол 2007;2:35—40.</mixed-citation><mixed-citation xml:lang="ru">Мисюрин А.В., Аксенова Е.В., Крутов А.А. и др. Молекулярная диагностика хронического миелолейкоза. Гематол трансфузиол 2007;2:35—40.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">12. Челышева Е.Ю., Туркина А.Г., Мисюрин А.В., Захарова А.В. Раннее выявление цитогенетического рецидива при динамическом исследовании уровня BCR-ABL-транскрипта у больного хроническим миелолейкозом. Гематол трансфузиол 2007;2:50—1.</mixed-citation><mixed-citation xml:lang="ru">Челышева Е.Ю., Туркина А.Г., Мисюрин А.В., Захарова А.В. Раннее выявление цитогенетического рецидива при динамическом исследовании уровня BCR-ABL-транскрипта у больного хроническим миелолейкозом. Гематол трансфузиол 2007;2:50—1.</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">13. Kaeda S.A., Chase A., Goldman J.M. Cytogenetic and molecular monitoring of residual desease in chronic myeloid leukemia. Acta Hematol 2002;107:64—75.</mixed-citation><mixed-citation xml:lang="ru">Kaeda S.A., Chase A., Goldman J.M. Cytogenetic and molecular monitoring of residual desease in chronic myeloid leukemia. Acta Hematol 2002;107:64—75.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">14. Goldman J.M. Chronic myeloid leukemia-still a few questions. Exp Hematol 2004;32:2—10.</mixed-citation><mixed-citation xml:lang="ru">Goldman J.M. Chronic myeloid leukemia-still a few questions. Exp Hematol 2004;32:2—10.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">15. Marin D., Marktel S., Szydlo R. et al. Survival of patients with chronic phase chronic myeloid leukemia after failed response to interferon-alfa. Lancet 2003;362:617—9.</mixed-citation><mixed-citation xml:lang="ru">Marin D., Marktel S., Szydlo R. et al. Survival of patients with chronic phase chronic myeloid leukemia after failed response to interferon-alfa. Lancet 2003;362:617—9.</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">16. Hughes T., Branford S. Molecular monitoring of BCR—ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Reviews 2006;20:29—41.</mixed-citation><mixed-citation xml:lang="ru">Hughes T., Branford S. Molecular monitoring of BCR—ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Reviews 2006;20:29—41.</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">17. Hughes T., Deininger M., Hochhaus A. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28—37.</mixed-citation><mixed-citation xml:lang="ru">Hughes T., Deininger M., Hochhaus A. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28—37.</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">18. Kawasaki E.S., Clark S.S., Coyne N.Y. et al. Diagnosis of chronic myelogenous and acute lymphocytic leukemias by detection of leukemia specific mRNA sequences amplified in vitro. Proc Nat Acad Sci USA 1988;85:5698—702.</mixed-citation><mixed-citation xml:lang="ru">Kawasaki E.S., Clark S.S., Coyne N.Y. et al. Diagnosis of chronic myelogenous and acute lymphocytic leukemias by detection of leukemia specific mRNA sequences amplified in vitro. Proc Nat Acad Sci USA 1988;85:5698—702.</mixed-citation></citation-alternatives></ref><ref id="B19"><label>19.</label><citation-alternatives><mixed-citation xml:lang="en">19. Morgan G.J., Hughes T., Janssen J.W.G. et al. Polymerase chain reaction for detection of residual leukaemia. Lancet 1989;1:928—9.</mixed-citation><mixed-citation xml:lang="ru">Morgan G.J., Hughes T., Janssen J.W.G. et al. Polymerase chain reaction for detection of residual leukaemia. Lancet 1989;1:928—9.</mixed-citation></citation-alternatives></ref><ref id="B20"><label>20.</label><citation-alternatives><mixed-citation xml:lang="en">20. Hughes T.P., Morgan G.J., Martiat P. et al. Detection of residual leukemia after bone marrow transplantation: role of PCR in predicting relapse. Blood 1991;77:874—8.</mixed-citation><mixed-citation xml:lang="ru">Hughes T.P., Morgan G.J., Martiat P. et al. Detection of residual leukemia after bone marrow transplantation: role of PCR in predicting relapse. Blood 1991;77:874—8.</mixed-citation></citation-alternatives></ref><ref id="B21"><label>21.</label><citation-alternatives><mixed-citation xml:lang="en">21. Hughes T., Kaeda J., Branford S. et al. Frequency of major molecular response to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003;349:1423—32.</mixed-citation><mixed-citation xml:lang="ru">Hughes T., Kaeda J., Branford S. et al. Frequency of major molecular response to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003;349:1423—32.</mixed-citation></citation-alternatives></ref><ref id="B22"><label>22.</label><citation-alternatives><mixed-citation xml:lang="en">22. Branford S., Hughes T.P., 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—99.</mixed-citation><mixed-citation xml:lang="ru">Branford S., Hughes T.P., 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—99.</mixed-citation></citation-alternatives></ref><ref id="B23"><label>23.</label><citation-alternatives><mixed-citation xml:lang="en">23. Merx K., Muller M.C., 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 alfa. Leukemia 2002;16:1579—83.</mixed-citation><mixed-citation xml:lang="ru">Merx K., Muller M.C., 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 alfa. Leukemia 2002;16:1579—83.</mixed-citation></citation-alternatives></ref><ref id="B24"><label>24.</label><citation-alternatives><mixed-citation xml:lang="en">24. Branford S., Rudzki Z., Harper A. et al. Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia 2003;17:2401—9.</mixed-citation><mixed-citation xml:lang="ru">Branford S., Rudzki Z., Harper A. et al. Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Leukemia 2003;17:2401—9.</mixed-citation></citation-alternatives></ref><ref id="B25"><label>25.</label><citation-alternatives><mixed-citation xml:lang="en">25. Wang L., Pearson K., Ferguson J.E. et al. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol 2003;120: 990—9.</mixed-citation><mixed-citation xml:lang="ru">Wang L., Pearson K., Ferguson J.E. et al. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol 2003;120: 990—9.</mixed-citation></citation-alternatives></ref><ref id="B26"><label>26.</label><citation-alternatives><mixed-citation xml:lang="en">26. O'Brien S., Guilhot F., Larson R. 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.</mixed-citation><mixed-citation xml:lang="ru">O'Brien S., Guilhot F., Larson R. 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.</mixed-citation></citation-alternatives></ref><ref id="B27"><label>27.</label><citation-alternatives><mixed-citation xml:lang="en">27. Branford S., Rudzki Z., Walsh S. et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 2003;102:276—83.</mixed-citation><mixed-citation xml:lang="ru">Branford S., Rudzki Z., Walsh S. et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 2003;102:276—83.</mixed-citation></citation-alternatives></ref><ref id="B28"><label>28.</label><citation-alternatives><mixed-citation xml:lang="en">28. Shah N., Nicoll J., Nagar B. et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2002;2:117—25.</mixed-citation><mixed-citation xml:lang="ru">Shah N., Nicoll J., Nagar B. et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2002;2:117—25.</mixed-citation></citation-alternatives></ref><ref id="B29"><label>29.</label><citation-alternatives><mixed-citation xml:lang="en">29. Gambacorti-Passerini C., Gunby R., Piazza R. et al. Molecular mechanisms of resistance to imatinib in Philadelphia chromosome-positive leukaemias. Lancet Oncol 2003;4:75—85.</mixed-citation><mixed-citation xml:lang="ru">Gambacorti-Passerini C., Gunby R., Piazza R. et al. Molecular mechanisms of resistance to imatinib in Philadelphia chromosome-positive leukaemias. Lancet Oncol 2003;4:75—85.</mixed-citation></citation-alternatives></ref><ref id="B30"><label>30.</label><citation-alternatives><mixed-citation xml:lang="en">30. Kreill S., Mueller M., Hanfstein B. et al. Management and clinical outcome of CML patients after imatinib resistance associated with ABL kinase domain mutations. Blood 2003;102:71.</mixed-citation><mixed-citation xml:lang="ru">Kreill S., Mueller M., Hanfstein B. et al. Management and clinical outcome of CML patients after imatinib resistance associated with ABL kinase domain mutations. Blood 2003;102:71.</mixed-citation></citation-alternatives></ref><ref id="B31"><label>31.</label><citation-alternatives><mixed-citation xml:lang="en">31. Shah N., Sawyers C. Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. Oncogene 2003;22:7389—95.</mixed-citation><mixed-citation xml:lang="ru">Shah N., Sawyers C. Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. Oncogene 2003;22:7389—95.</mixed-citation></citation-alternatives></ref><ref id="B32"><label>32.</label><citation-alternatives><mixed-citation xml:lang="en">32. Al-Ali H., Heinrich M., Lange T. et al. High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol J 2004;5:55—60.</mixed-citation><mixed-citation xml:lang="ru">Al-Ali H., Heinrich M., Lange T. et al. High incidence of BCR-ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib. Hematol J 2004;5:55—60.</mixed-citation></citation-alternatives></ref><ref id="B33"><label>33.</label><citation-alternatives><mixed-citation xml:lang="en">33. Hochhaus A., La Rosee P. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 2004;18:1321—31.</mixed-citation><mixed-citation xml:lang="ru">Hochhaus A., La Rosee P. Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance. Leukemia 2004;18:1321—31.</mixed-citation></citation-alternatives></ref><ref id="B34"><label>34.</label><citation-alternatives><mixed-citation xml:lang="en">34. Soverini S., Colarossi S., Gnani A. et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 2006;12(24):7374—9.</mixed-citation><mixed-citation xml:lang="ru">Soverini S., Colarossi S., Gnani A. et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 2006;12(24):7374—9.</mixed-citation></citation-alternatives></ref><ref id="B35"><label>35.</label><citation-alternatives><mixed-citation xml:lang="en">35. Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematology Am Soc Hematol Educ Program 2007:376—83.</mixed-citation><mixed-citation xml:lang="ru">Branford S. Chronic myeloid leukemia: molecular monitoring in clinical practice. Hematology Am Soc Hematol Educ Program 2007:376—83.</mixed-citation></citation-alternatives></ref><ref id="B36"><label>36.</label><citation-alternatives><mixed-citation xml:lang="en">36. Hughes T., Deininger M., Hochhaus A. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28—37.</mixed-citation><mixed-citation xml:lang="ru">Hughes T., Deininger M., Hochhaus A. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28—37.</mixed-citation></citation-alternatives></ref><ref id="B37"><label>37.</label><citation-alternatives><mixed-citation xml:lang="en">37. Hochhaus A., Kreil S., Corbin A. et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002;16:2190—6.</mixed-citation><mixed-citation xml:lang="ru">Hochhaus A., Kreil S., Corbin A. et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002;16:2190—6.</mixed-citation></citation-alternatives></ref><ref id="B38"><label>38.</label><citation-alternatives><mixed-citation xml:lang="en">38. Roche-Lestienne C., Soenen-Cornu V., Grardel-Duflos N. et al. Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood 2002;100:1014—8.</mixed-citation><mixed-citation xml:lang="ru">Roche-Lestienne C., Soenen-Cornu V., Grardel-Duflos N. et al. Several types of mutations of the Abl gene can be found in chronic myeloid leukemia patients resistant to STI571, and they can pre-exist to the onset of treatment. Blood 2002;100:1014—8.</mixed-citation></citation-alternatives></ref><ref id="B39"><label>39.</label><citation-alternatives><mixed-citation xml:lang="en">39. Sattler M., Verma S., Shrikhande G. et al. The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells. J Biol Chem 2000;275(32):24273—8.</mixed-citation><mixed-citation xml:lang="ru">Sattler M., Verma S., Shrikhande G. et al. The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells. J Biol Chem 2000;275(32):24273—8.</mixed-citation></citation-alternatives></ref><ref id="B40"><label>40.</label><citation-alternatives><mixed-citation xml:lang="en">40. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162(1):156—9.</mixed-citation><mixed-citation xml:lang="ru">Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162(1):156—9.</mixed-citation></citation-alternatives></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">41. 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;104:2926—32.</mixed-citation><mixed-citation xml:lang="ru">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;104:2926—32.</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><citation-alternatives><mixed-citation xml:lang="en">42. Branford S., Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. Methods Mol Med 2006;125:69—92.</mixed-citation><mixed-citation xml:lang="ru">Branford S., Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. Methods Mol Med 2006;125:69—92.</mixed-citation></citation-alternatives></ref><ref id="B43"><label>43.</label><citation-alternatives><mixed-citation xml:lang="en">43. Burgess M., Skaggs B., Shah N. et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA 2005;102:3395—400.</mixed-citation><mixed-citation xml:lang="ru">Burgess M., Skaggs B., Shah N. et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA 2005;102:3395—400.</mixed-citation></citation-alternatives></ref><ref id="B44"><label>44.</label><citation-alternatives><mixed-citation xml:lang="en">44. Corbin A., La Rose P., Stoffregen E. et al. Several BCR-ABL kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 2003;101(11):4611—4.</mixed-citation><mixed-citation xml:lang="ru">Corbin A., La Rose P., Stoffregen E. et al. Several BCR-ABL kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 2003;101(11):4611—4.</mixed-citation></citation-alternatives></ref><ref id="B45"><label>45.</label><citation-alternatives><mixed-citation xml:lang="en">45. O'Hare T., Eide C.A., Deininger M. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 2007;110(7):2242—9.</mixed-citation><mixed-citation xml:lang="ru">O'Hare T., Eide C.A., Deininger M. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 2007;110(7):2242—9.</mixed-citation></citation-alternatives></ref><ref id="B46"><label>46.</label><citation-alternatives><mixed-citation xml:lang="en">46. O'Hare T., Walters D., Stoffregen E. et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:4500—5.</mixed-citation><mixed-citation xml:lang="ru">O'Hare T., Walters D., Stoffregen E. et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res 2005;65:4500—5.</mixed-citation></citation-alternatives></ref><ref id="B47"><label>47.</label><citation-alternatives><mixed-citation xml:lang="en">47. Gorre M., 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—80.</mixed-citation><mixed-citation xml:lang="ru">Gorre M., 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—80.</mixed-citation></citation-alternatives></ref></ref-list></back></article>
