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.
Caterina De BenedittisCristina PapayannidisClaudia VenturiMaria Chiara AbbenanteStefania PaoliniSarah ParisiChiara SartorMichele CavoGiovanni MartinelliSimona SoveriniPublished in: BMC cancer (2017)
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.
Keyphrases
- chronic myeloid leukemia
- tyrosine kinase
- acute lymphoblastic leukemia
- amino acid
- epidermal growth factor receptor
- allogeneic hematopoietic stem cell transplantation
- single cell
- photodynamic therapy
- stem cells
- acute myeloid leukemia
- bone marrow
- mesenchymal stem cells
- drug delivery
- locally advanced
- smoking cessation