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  1. bookVolume 21 (2013): Edition 1 (March 2013)
Revista Romana de Medicina de Laborator's Cover Image
Revista Romana de Medicina de Laborator
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Magazine
eISSN
2284-5623
ISSN
2284-5623
Première parution
08 Aug 2013
Périodicité
4 fois par an
Langues
Anglais
access type Accès libre

Tyrosine kinase inhibitor treatment outcome in a single center cohort of chronic myeloid leukemia patients. The role of the T315I ABL kinase domain mutation

Delia Dima,
Delia Dima,
Adrian P. Trifa,
Adrian P. Trifa,
Mariana Paţiu,
Mariana Paţiu,
Cristian S. Vesa,
Cristian S. Vesa,
Ioana C. Frinc,
Ioana C. Frinc,
Ljubomir Petrov et
Ljubomir Petrov et
Andrei Cucuianu
Andrei Cucuianu
Publié en ligne: 08 Aug 2013
Volume & Edition: Volume 21 (2013) - Edition 1 (March 2013)
Pages: 29 - 37
Revista Romana de Medicina de Laborator's Cover Image
Revista Romana de Medicina de Laborator
Détails du magazine
License
Format
Magazine
eISSN
2284-5623
ISSN
2284-5623
Première parution
08 Aug 2013
Périodicité
4 fois par an
Langues
Anglais
Abstract

Introduction. Since the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), a dramatic improvement in hematologic, cytogenetic and molecular responses was noted. Also, the overall survival increased significantly. Unfortunately, in certain patients, resistance to TKI develops relatively early, especially due to point mutations in the ABL kinase domain, among which the T315I mutation confers resistance to all three currently available TKIs (imatinib, dasatinib, nilotinib). Methods. We performed a prospective study on 74 patients diagnosed with chronic phase CML, for whom we analyzed the T315I mutation. Mutational analysis was performed using ARMS-PCR (with subsequent confirmation by direct sequencing) at regular intervals of 6 months or in case of suboptimal response, loss of response or progression. Correlations between the T315I mutation and disease characteristics, response to treatment and survival were analyzed. A comparative analysis between patients positive and negative for the mutation was performed. The patients were followed and evaluated according to European Leukemia Net (ELN) criteria. Results. T315I mutation was detected in 3 patients (4.05%) and its presence was correlated with younger age at diagnosis, second line TKI therapy, progressive disease and decreased survival from the moment of detection. Conclusions. ARMS-PCR is a sensitive, easy to use method for the detection of T315I mutation in chronic phase CML patients

Keywords

  • Chronic myeloid leukemia
  • mutation
  • T315I
  • imatinib

Cuvinte cheie

  • leucemie mieloidă cronică
  • mutaţie
  • T315I
  • imatinib

1. Lichtman LA, Liesveld JL. CML and related disorders, in Williams Hematology, McGraw Hill 8th edition, 1085-1124.Search in Google Scholar

2. Petrov L, Cucuianu A, Bojan A, Urian L. Leucemia granulocitara cronica. In “Hematologie Clinica”. Casa Cartii de Stiinta, Cluj-Napoca, 2009: 45-63Search in Google Scholar

3. Apperley JF. Mechanism of resistance to imatinib in chronic myeloid leukemia. Lancet Oncol, 2007, 8:1018-102910.1016/S1470-2045(07)70342-XSearch in Google Scholar

4. Quintas-Guardama A, Kantarjian H, Cortes J. Mechanism of primary and secondary resistance to imatinib in chronic myeloid leukemia. Cancer Control, 2009, 16: 122-131.10.1177/10732748090160020419337198Search in Google Scholar

5. Bixby D, Talpaz M. Mechanism of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology 2009, 1: 461-47610.1182/asheducation-2009.1.46120008232Search in Google Scholar

6. Nicolini FE, Corm S, Le QH, Sorel N, Hayette S, Bories D et al. Mutation status and clinical outcome of 89 imatinib mesylate- resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML. Leukemia 2006, 20: 1061-106610.1038/sj.leu.240423616642048Search in Google Scholar

7. Nicolini FE, Hayette S, Corm S, Bachy E, Bories D, Tulliez M et al. Clinical outcome of 27 imatinib mesylate resistant chronic myelogenous leukemia patients harboring T315I BCR-ABL mutation. The Hematology Journal 2007, 92: 1238-124110.3324/haematol.1136917768119Search in Google Scholar

8. Nicolini FE, Mauro MJ, Martinelli G, Kim DW, Soverini S, Muller MC et al. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood, 2009, 114: 5271-5278.10.1182/blood-2009-04-219410491693919843886Search in Google Scholar

9. Hughes T, Saglio G, Branford S, Soverini S, Kim DW, Muller MC et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol, 2009, 27: 4204-421010.1200/JCO.2009.21.8230497923019652056Search in Google Scholar

10. Muller Mc, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R et al. Dasatinib treatment of chronic phase chronic myeloid leukemia, analysis of responses according to preexisting BCR-ABL mutations. Blood, 2009, 114:4944-495310.1182/blood-2009-04-214221491694019779040Search in Google Scholar

11. Goldman JM. How I treat chronic myeloid leukemia in the imatinib era. Blood, 2007, 110: 2828-3710.1182/blood-2007-04-03894317626839Search in Google Scholar

12. Roche-Lestienne C, Soenen-Cornu V, Grardel- Duflos N, Laï JL, Philippe N, Facon T et all. 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, 100:1014-101810.1182/blood.V100.3.1014Search in Google Scholar

13. Khorashad JS, Thelwell N, Milojkovic D, Marin D, Watson JA, Goldman JM, Apperley JF et al. A new rapid and sensitive assay for detecting the chronic myeloid leukemia T315I BCR-ABL kinase domain mutation in chronic myeloid leukemia. J Clin Pathol. 2008, 61, 863-86510.1136/jcp.2008.05680418587017Search in Google Scholar

14. Y M Dennis Lo. The amplification refractory mutation system. Methods in Molecular Medicine, 1998, 16: 61-69Search in Google Scholar

15. Dima D, Trifa AP, Cucuianu A, Popp RA, Patiu M, Petrov L. Monitoring T315I mutation in chronic myeloid leukemia by amplification refractory mutation system PCR. Rev Rom de Med de Lab, 2008, 13:17-20Search in Google Scholar

16. Marin D, Ibrahim Amr R, Goldman JM. European treatment and outcome study (EUTOS) score for chronic myeloid leukemia still requires more confirmation. J Clin Oncol, 2011, 29: 3944-394510.1200/JCO.2011.37.696221900102Search in Google Scholar

17. Cortes J, Lipton JH, Rea D, Diqumarti R, Chuah C, Nanda N et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with CML with T315I mutation. Blood, 2012, 120:2573-258010.1182/blood-2012-03-415307491658322896000Search in Google Scholar

18. Wei G, Rafiyath S and Liu D. First line treatment of chronic myeloid leukemia: dasatinib, nilotinib or imatinib. J Hematol Oncol, 2010, 3: 47-5210.1186/1756-8722-3-47300036921108851Search in Google Scholar

19. Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I et al. Ponatinib in refractory Philadelphia chromosome- positive leukemias. N Eng J Med, 2012, 367:2075-8810.1056/NEJMoa1205127377738323190221Search in Google Scholar

20. Soverini S, Hochhaus A, Nicolini FE, Gruber F, Lange T, Saglio G, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood, 2011, 118:1208-1215 10.1182/blood-2010-12-32640521562040Search in Google Scholar

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