Jan 17, 2013 · BCR-ABL1 compound mutations can confer high-level resistance to imatinib and other ABL1 tyrosine kinase inhibitors (TKIs). The third-generation ABL1 TKI ponatinib is effective against BCR-ABL1 point mutants individually, but remains vulnerable to certain BCR-ABL1 compound mutants.

Nov 16, 2008 · Our study suggests that the incidence of certain BCR-ABL kinase domain mutations may vary in different ethnic origins and that this variation may be related to different pharmacokinetic profiles. This observation may have important implications for planning and monitoring the ideal therapeutic IM dose for CML patients from different ethnicities.

ABL1 M351T lies within the protein kinase domain of the Abl1 protein (UniProt.org). M351T results in loss of inhibitor binding (PMID: 24456693) and decreased kinase activity in cell culture (PMID: 33820471), has been demonstrated to occur as a secondary resistance mutation (PMID: 16046538, PMID: 16880519), and in the context of BCR-ABL1 leads ...

Of the BCR-ABL1 dependent mechanisms, mutations in the tyrosine kinase domain (TKD) are the commonest cause of resistance. Allele specific oligonucleotide - polymerase chain reaction (ASO-PCR) was done for testing the six common TKD mutations, T315I, G250E, E255K, M244V, M351T, and Y253F. TKD mutation study was done on 83 patients.

PCR and sequencing were used to detect mutations in the ABL1 kinase region of BCR-ABL1. Total RNA was reverse-transcribed into cDNA and then amplified with Platinum Taq Polymerase High Fidelity (Thermo Fisher Scientific, Inc.).

We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib.

Feb 16, 2024 · M351T (rs121913457), E255K (rs387906517), and Y253H (rs121913461) are of particular clinical significance due to their association with high-level imatinib resistance. This study was conducted to investigate the potential role of three significant SNPs in CML progression due to IM resistance.

M351T was the most frequently detected mutation both alone and concomitantly with other mutations, being present in 5 (71%) of 7 patients carrying more than one BCR-ABL1 mutation. M351T maps to the activation loop hinge and has lower kinase activity, growth competition potential in low serum, B-lymphoid transformation potency and colony ...

Jan 1, 2014 · Findings from several studies indicate that BCR-ABL1 mutations are detected with a frequency ranging from 12% to 63% in CML patients who experienced imatinib resistance (Table 2). The most common mutations with imatinib were T315I, G250E, M244V, M351T, and …

Nov 16, 2008 · In this study, direct sequencing of the BCR-ABL kinase domain was performed in 94 IM-R CML patients of different Asian ethnicities (52% Chinese, 19% Malay, 18% Indian and 11% of other Asian ethnic origins).