دورية أكاديمية
The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report
| العنوان: | The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report |
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| المؤلفون: | De Benedittis, Caterina, Papayannidis, Cristina, Venturi, Claudia, Abbenante, Maria Chiara, Paolini, Stefania, Parisi, Sarah, Sartor, Chiara, Cavo, Michele, Martinelli, Giovanni, Soverini, Simona |
| المصدر: | BMC Cancer 17(1) 523 |
| سنة النشر: | 2017 |
| المجموعة: | Zenodo |
| مصطلحات موضوعية: | BCR-ABL1 mutation, T315I mutation, Ph+ Acute Lymphoblastic Leukemia, Resistance, Case Report, Relapse, Dasatinib, Ponatinib, Transplant, Blinatumomab |
| الوصف: | Background: The treatment of Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL) patients who harbor the T315I BCR-ABL1 mutation or who have two or more mutations in the same BCR-ABL1 molecule is particularly challenging since first and second-generation Tyrosine Kinase Inhibitors (TKIs) are ineffective. Ponatinib, blinatumomab, chemotherapy and transplant are the currently available options in these cases.Case presentation: We here report the case of a young Ph+ ALL patient who relapsed on front-line dasatinib therapy because of two independent T315I-positive subclones, resulting from different nucleotide substitutions -one of whom never reported previously- and where additional mutant clones outgrew and persisted despite ponatinib, transplant, blinatumomab and conventional chemotherapy. Deep Sequencing (DS) was used to dissect the complexity of BCR-ABL1 kinase domain (KD) mutation status and follow the kinetics of different mutant clones across the sequential therapeutic approaches.Conclusions: This case presents several peculiar and remarkable aspects: i) distinct clones may acquire the same amino acid substitution via different nucleotide changes; ii) the T315I mutation may arise also from an 'act' to 'atc' codon change; iii) the strategy of temporarily replacing TKI therapy with chemo or immunotherapy, in order to remove the selective pressure and deselect aggressive mutant clones, cannot always be expected to be effective; iv) BCR-ABL1-mutated sub-clones may persist at very low levels (undetectable even by Deep Sequencing) for long time and then outcompete BCR-ABL1-unmutated ones becoming dominant even in the absence of any TKI selective pressure. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | info:eu-repo/grantAgreement/EC/FP7/306242/; https://zenodo.org/communities/fp7-bmcTest; https://zenodo.org/record/839575Test; https://doi.org/10.1186/s12885-017-3511-2Test; oai:zenodo.org:839575 |
| DOI: | 10.1186/s12885-017-3511-2 |
| الإتاحة: | https://doi.org/10.1186/s12885-017-3511-2Test https://zenodo.org/record/839575Test |
| حقوق: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0/legalcodeTest |
| رقم الانضمام: | edsbas.3E85FD87 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12885-017-3511-2 |
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