TY - JOUR
T1 - BCR-ABL V280G mutation, potential role in imatinib resistance: First case report
AU - Azevedo, A.P.
AU - Reichert, A.
AU - Afonso, C.
AU - Alberca, M.D.
AU - Tavares, P.
AU - Lima, F.
N1 - Export Date: 28 December 2017
Correspondence Address: Azevedo, A.P.; Department of Clinical Pathology, Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Estrada do Forte do Alto do Duque, Portugal; email: [email protected]
Chemicals/CAS: glycine, 56-40-6, 6000-43-7, 6000-44-8; hydroxyurea, 127-07-1; imatinib, 152459-95-5, 220127-57-1; nilotinib, 641571-10-0; valine, 7004-03-7, 72-18-4
References: Radich, J.P., Shah, N.P., Mauro, M.J., Integrating current treatment options for TKIresistant chronic myeloid leukemia (2014) Clin Adv Hematol Oncol, 12 (11), pp. 3-17; Savona, M.R., Molecular monitoring and minimal residual disease in the management of chronic myelogenous leukemia (2014) J Community Support Oncol, 12, pp. 171-178; Kantarjian, H.M., Cortes, J., La Rosée, P., Hochhaus, A., Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase (2010) Cancer, 116, pp. 1419-1430; Weisberg, E., Manley, P.W., Cowan-Jacob, S.W., Hochhaus, A., Griffin, J.D., Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia (2007) Nat Rev Cancer, 7, pp. 345-356; Nicolini, F.E., Corm, S., Lê, Q.H., Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: A retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP) (2006) Leukemia, 20, pp. 1061-1066; Soverini, S., Colarossi, S., Gnani, A., 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 (2006) Clin Cancer Res, 12, pp. 7374-7379; Sokal, J.E., Cox, E.B., Baccarani, M., Prognostic discrimination in “good-risk” chronic granulocytic leukemia (1984) Blood, 63, pp. 789-799; Hasford, J., Pfirrmann, M., Hehlmann, R., A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group (1998) J Natl Cancer Inst, 90, pp. 850-858; Hasford, J., Baccarani, M., Hoffmann, V., Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: The EUTOS score (2011) Blood, 118, pp. 686-692; Gromicho, M., Magalhães, M., Torres, F., Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib (2013) Oncol Rep, 29, pp. 741-750; Liu, L.L., Li, F., Pao, W., Michor, F., Dose-dependent mutation rates determine optimum erlotinib dosing strategies for EGFR mutant non-small cell lung cancer patients (2015) Plos ONE, 10; Tang, C., Schafranek, L., Watkins, D.B., Tyrosine kinase inhibitor resistance in chronic myeloid leukemia cell lines: Investigating resistance pathways (2011) Leuk Lymphoma, 52, pp. 2139-2147; Hayakawa, H., Ichihara, E., Ohashi, K., Lower gefitinib dose led to earlier resistance acquisition before emergence of T790M mutation in epidermal growth factor receptor-mutated lung cancer model (2013) Cancer Sci, 104, pp. 1440-1446; Santos, F.P., Kantarjian, H., Fava, C., Clinical impact of dose reductions and interruptions of second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia (2010) Br J Haematol, 150, pp. 303-312; Van Obbergh, F., Knoops, L., Devos, T., The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study [published online ahead of print December 22, 2016] Clin Biochem; Vine, J., Cohen, S.B., Ruchlemer, R., Polymorphisms in the human organic cation transporter and the multidrug resistance gene: Correlation with imatinib levels and clinical course in patients with chronic myeloid leukemia (2014) Leuk Lymphoma, 55, pp. 2525-2531; Sundar, H., Radich, J., Optimizing patient care in chronic phase Chronic Myelogenous Leukemia: A multidisciplinary approach (2016) J Natl Compr Cancer Netw, 14, pp. s1-s6; McDougall, J., Ramsey, S.D., Radich, J., What happens when imatinib goes generic? (2016) J Natl Compr Canc Netw, 14, pp. 128-131; Hochhaus, A., Saglio, G., Hughes, T.P., Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial (2016) Leukemia, 30, pp. 1044-1054; Cortes, J.E., Saglio, G., Kantarjian, H.M., Final 5-year study results of DASISION: The dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial (2016) J Clin Oncol, 34, pp. 2333-2340; Druker, B.J., Guilhot, F., O’Brien, S.G., Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia (2006) N Engl J Med, 355, pp. 2408-2417; Soverini, S., De Benedittis, C., Mancini, M., Martinelli, G., Mutations in the BCRABL1 kinase domain and elsewhere in chronic myeloid leukemia (2015) Clin Lymphoma Myeloma Leuk, 15, pp. S120-S128; O’Brien, S., Radich, J.P., Abboud, C.N., Chronic myelogenous leukemia, version 1.2015 (2014) J Natl Compr Canc Netw, 12, pp. 1590-1610; Baccarani, M., Deininger, M.W., Rosti, G., European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013 (2013) Blood, 122, pp. 872-884; Deininger, M.W., Molecular monitoring in CML and the prospects for treatmentfree remissions (2015) Hematology am Soc Hematol Educ Program, 2015, pp. 257-263; Soverini, S., Hochhaus, A., Nicolini, F.E., 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 (2011) Blood, 118, pp. 1208-1215; Soverini, S., Branford, S., Nicolini, F.E., Implications of BCR-ABL1 kinase domain- mediated resistance in chronic myeloid leukemia (2014) Leuk Res, 38, pp. 10-20; Machova Polakova, K., Kulvait, V., Benesova, A., Next-generation deep sequencing improves detection of BCR-ABL1 kinase domain mutations emerging under tyrosine kinase inhibitor treatment of chronic myeloid leukemia patients in chronic phase (2015) J Cancer Res Clin Oncol, 141, pp. 887-899; Jabbour, E., Saglio, G., Hughes, T.P., Kantarjian, H., Suboptimal responses in chronic myeloid leukemia: Implications and management strategies (2012) Cancer, 118, pp. 1181-1191; Gruber, T.A., Chang, M.S., Sposto, R., Müschen, M., Activation-induced cytidine deaminase accelerates clonal evolution in BCR-ABL1-driven B-cell lineage acute lymphoblastic leukemia (2010) Cancer Res, 70, pp. 7411-7420
PY - 2017
Y1 - 2017
N2 - Introduction: The identification of BCR-ABL expression as the defining leukemogenic event in chronic myeloid leukemia (CML) and the introduction of BCR-ABL tyrosine kinase inhibitors in 2001 have revolutionized disease management, leading to a reduction in mortality rates and accordingly an increase in the estimated prevalence of CML. Case report: Based on medical records and clinical follow-up, the authors present the case of a Philadelphia chromosome–positive CML patient who developed resistance to imatinib. Quantitative reverse transcription-polymerase chain reaction testing revealed a V280G BCR-ABL mutation. Discussion and conclusions: This is the first report describing a new BCR-ABL kinase domain mutation—V280G—that might be associated with resistance to imatinib. Approximately 15% to 30% of patients treated with imatinib discontinue treatment due to resistance or intolerance. More than 90 BCR-ABL mutations were detected so far, conferring variable degrees of drug resistance, with consequent clinical, therapeutic, and prognostic impact. © The Author(s) 2017.
AB - Introduction: The identification of BCR-ABL expression as the defining leukemogenic event in chronic myeloid leukemia (CML) and the introduction of BCR-ABL tyrosine kinase inhibitors in 2001 have revolutionized disease management, leading to a reduction in mortality rates and accordingly an increase in the estimated prevalence of CML. Case report: Based on medical records and clinical follow-up, the authors present the case of a Philadelphia chromosome–positive CML patient who developed resistance to imatinib. Quantitative reverse transcription-polymerase chain reaction testing revealed a V280G BCR-ABL mutation. Discussion and conclusions: This is the first report describing a new BCR-ABL kinase domain mutation—V280G—that might be associated with resistance to imatinib. Approximately 15% to 30% of patients treated with imatinib discontinue treatment due to resistance or intolerance. More than 90 BCR-ABL mutations were detected so far, conferring variable degrees of drug resistance, with consequent clinical, therapeutic, and prognostic impact. © The Author(s) 2017.
KW - BCR-ABL
KW - CML
KW - Imatinib
KW - Mutation
KW - Nilotinib
KW - alpha interferon
KW - BCR ABL protein
KW - glycine
KW - hydroxyurea
KW - imatinib
KW - nilotinib
KW - valine
KW - aged
KW - amino acid substitution
KW - Article
KW - BCR ABL gene
KW - case report
KW - chromosome 22
KW - chromosome 9
KW - chronic myeloid leukemia
KW - clinical article
KW - disease course
KW - drug dose escalation
KW - drug withdrawal
KW - EUTOS score
KW - female
KW - gene
KW - gene mutation
KW - gene sequence
KW - Hasford score
KW - human
KW - leukoderma
KW - reverse transcription polymerase chain reaction
KW - Sokal score
KW - splenomegaly
U2 - 10.1177/1179554917702870
DO - 10.1177/1179554917702870
M3 - Article
C2 - 28469513
SN - 1179-5549
VL - 11
JO - Clinical Medicine Insights: Oncology
JF - Clinical Medicine Insights: Oncology
M1 - 1179554917702870
ER -
