Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016)
Background. Kinase domain mutations of BCR-ABL gene is the most common cause of tyrosine kinase inhibitor resistance. Aim. To present the data on prognostic value of BCR-ABL mutation burden in Russian patients over the last 10 years. Materials & Methods. The study included 1885 chronic mye...
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| Format: | Article |
| Language: | Russian |
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Practical Medicine Publishing House
2018-07-01
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| Series: | Клиническая онкогематология |
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| Online Access: | http://bloodjournal.ru/wp-content/uploads/2018/06/3-2.pdf |
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| author | VV Tikhonova MA Isakov VA Misyurin YuP Finashutina LA Kesaeva NA Lyzhko IN Soldatova NN Kasatkina EN Misyurina AV Misyurin |
| author_facet | VV Tikhonova MA Isakov VA Misyurin YuP Finashutina LA Kesaeva NA Lyzhko IN Soldatova NN Kasatkina EN Misyurina AV Misyurin |
| author_sort | VV Tikhonova |
| collection | DOAJ |
| description | Background. Kinase domain mutations of BCR-ABL gene is the most common cause of tyrosine kinase inhibitor resistance.
Aim. To present the data on prognostic value of BCR-ABL mutation burden in Russian patients over the last 10 years.
Materials & Methods. The study included 1885 chronic myeloid leukemia (CML) patients with tyrosine kinase inhibitor resistance who were followed up from 2006 to 2016. BCR-ABL point mutations in mRNA samples were analyzed by means of polymerase chain reaction and subsequent Sanger sequencing.
Results. In 1257 CML patients with signs of tyrosine kinase inhibitor resistance BCR-ABL expression level was > 1 %. BCR–ABL mutations were detected in 31.8 % of patients. Total mutation count was 467 (70 mutation types). Total count of patients with mutation-associated tyrosine kinase inhibitor resistance decreased from 36.6 % (2006–2008) to 24.95 % (2013–2016) and to marked decrease of 23.12 % in 2014. Detection rate of imatinib-resistant mutations and F359V mutation was shown to decrease within the period from 2010–2011 to 2014–2015. F317L level, which is responsible for dasatinib resistance, considerably increased in 2015. T315I frequency was the highest in 2014, afterwards it was gradually decreasing. Mutation-associated resistance rates varied by region of the Russian Federation.
Conclusion. The analysis of trends of mutation incidence in patients with CML can be of extreme significance in long-term prognosis of resistance development and in improvement of treatment planning. |
| format | Article |
| id | doaj-art-debf19c21fe34eca8525d68f8d15418f |
| institution | Kabale University |
| issn | 1997-6933 2500-2139 |
| language | Russian |
| publishDate | 2018-07-01 |
| publisher | Practical Medicine Publishing House |
| record_format | Article |
| series | Клиническая онкогематология |
| spelling | doaj-art-debf19c21fe34eca8525d68f8d15418f2025-08-20T03:24:57ZrusPractical Medicine Publishing HouseКлиническая онкогематология1997-69332500-21392018-07-0111322723310.21320/2500-2139-2018-11-3-227-233Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016)VV Tikhonova0MA Isakov1VA Misyurin2YuP Finashutina3LA Kesaeva4NA Lyzhko5IN Soldatova6NN Kasatkina7EN Misyurina8AV Misyurin9NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; GenoTekhnologiya, 104 Profsoyuznaya str., Moscow, Russian Federation, 117485Aston Consulting, 31g Shabolovka str., Moscow, Russian Federation, 115162NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; GenoTekhnologiya, 104 Profsoyuznaya str., Moscow, Russian Federation, 117485NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; GenoTekhnologiya, 104 Profsoyuznaya str., Moscow, Russian Federation, 117485NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478GenoTekhnologiya, 104 Profsoyuznaya str., Moscow, Russian Federation, 117485NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478Municipal Clinical Hospital No. 52, 3 Pekhotnaya str., Moscow, Russian Federation, 123182NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Aston Consulting, 31g Shabolovka str., Moscow, Russian Federation, 115162Background. Kinase domain mutations of BCR-ABL gene is the most common cause of tyrosine kinase inhibitor resistance. Aim. To present the data on prognostic value of BCR-ABL mutation burden in Russian patients over the last 10 years. Materials & Methods. The study included 1885 chronic myeloid leukemia (CML) patients with tyrosine kinase inhibitor resistance who were followed up from 2006 to 2016. BCR-ABL point mutations in mRNA samples were analyzed by means of polymerase chain reaction and subsequent Sanger sequencing. Results. In 1257 CML patients with signs of tyrosine kinase inhibitor resistance BCR-ABL expression level was > 1 %. BCR–ABL mutations were detected in 31.8 % of patients. Total mutation count was 467 (70 mutation types). Total count of patients with mutation-associated tyrosine kinase inhibitor resistance decreased from 36.6 % (2006–2008) to 24.95 % (2013–2016) and to marked decrease of 23.12 % in 2014. Detection rate of imatinib-resistant mutations and F359V mutation was shown to decrease within the period from 2010–2011 to 2014–2015. F317L level, which is responsible for dasatinib resistance, considerably increased in 2015. T315I frequency was the highest in 2014, afterwards it was gradually decreasing. Mutation-associated resistance rates varied by region of the Russian Federation. Conclusion. The analysis of trends of mutation incidence in patients with CML can be of extreme significance in long-term prognosis of resistance development and in improvement of treatment planning.http://bloodjournal.ru/wp-content/uploads/2018/06/3-2.pdfchronic myeloid leukemiakinase domain mutations of BCR-ABL genetargeted therapyresistance |
| spellingShingle | VV Tikhonova MA Isakov VA Misyurin YuP Finashutina LA Kesaeva NA Lyzhko IN Soldatova NN Kasatkina EN Misyurina AV Misyurin Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016) Клиническая онкогематология chronic myeloid leukemia kinase domain mutations of BCR-ABL gene targeted therapy resistance |
| title | Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016) |
| title_full | Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016) |
| title_fullStr | Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016) |
| title_full_unstemmed | Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016) |
| title_short | Tyrosine Kinase Inhibitor Resistance in Patients with Chronic Myeloid Leukemia: A 10-Year Study of BCR-ABL Gene Mutation Profile in Russia (2006–2016) |
| title_sort | tyrosine kinase inhibitor resistance in patients with chronic myeloid leukemia a 10 year study of bcr abl gene mutation profile in russia 2006 2016 |
| topic | chronic myeloid leukemia kinase domain mutations of BCR-ABL gene targeted therapy resistance |
| url | http://bloodjournal.ru/wp-content/uploads/2018/06/3-2.pdf |
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