rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Preclinical development of a novel BCR-ABL T315I inhibitor against chronic myeloid leukemia.
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31837444 |
2020 |
rs121913459
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|
|
0.800 |
GeneticVariation |
BEFREE |
Taken together, we provide chronic myeloid leukemia tailored BCR-ABL1p210 and BCR-ABL1p210/T315I fly model which can be used to test new compounds with improved therapeutic indices.
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31101753 |
2020 |
rs121913459
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|
|
0.800 |
GeneticVariation |
BEFREE |
We also investigated the functional relevance of HMGCLL1 blockade with respect to response to TKI therapy and showed that small interfering RNA mediated blockade of HMGCLL1 isoform 3 results in significant decrease in viability of BCR-ABL1-positive cells including K562, CML-T1 or BaF3 cell lines with or without ABL1 kinase domain mutations such as T315I mutation.
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30555164 |
2019 |
rs121913459
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|
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0.800 |
GeneticVariation |
BEFREE |
Ponatinib is a third-generation TKI that is currently approved as per label when no other TKIs are indicated for the treatment of patients with CML and Ph+ ALL after failing treatment with second-generation TKIs or if presence of T315I mutation is discovered.
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30251548 |
2019 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Most remarkably, ATO/IFN significantly prolonged the survival of primary T315I-CML mice and displayed a dramatic impairment of disease engraftment in secondary mice, which reflected decreased LIC activity.
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31034603 |
2019 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
In chronic myeloid leukemia (CML), resistance against second-generation tyrosine kinase inhibitors (TKI) remains a serious clinical challenge, especially in the context of multi-resistant BCR-ABL1 mutants, such as T315I.
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30711891 |
2019 |
rs121913459
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|
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0.800 |
GeneticVariation |
BEFREE |
HU and the CDK4/CDK6-blocker palbociclib inhibit growth of CML clones expressing BCR-ABL1<sup>T315I</sup> or complex T315I-including compound-mutations.
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31761618 |
2019 |
rs121913459
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|
|
0.800 |
GeneticVariation |
BEFREE |
We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo-HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia.
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31785158 |
2019 |
rs121913459
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|
|
0.800 |
GeneticVariation |
BEFREE |
HQP1351, an orally bioavailable multikinase BCR-ABL inhibitor, is currently in clinical trials for the treatment of T315I mutant chronic myelogenous leukemia (CML), but the potential application in imatinib-resistant GISTs carrying secondary KIT mutations has not been explored.
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31673329 |
2019 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Discovery of (E)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)propanamide (CHMFL-ABL-121) as a highly potent ABL kinase inhibitor capable of overcoming a variety of ABL mutants including T315I for chronic myeloid leukemia.
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30317026 |
2018 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Alternative strategies to specifically target T315I-BCR-ABL are needed for the treatment of CML patients harboring such a mutation.
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29358661 |
2018 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Ponatinib induces a sustained deep molecular response in a chronic myeloid leukaemia patient with an early relapse with a T315I mutation following allogeneic hematopoietic stem cell transplantation: a case report.
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30526517 |
2018 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Ponatinib (AP24534) is currently the only approved CML drug that is active against the ABL1(T315I) mutation.
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29608815 |
2018 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Ponatinib is active against all BCR-ABL1 mutants, including T315I, and is widely used to treat patients who developed resistance to other TKIs in any CML phase; however, only limited data is available on the possible role of ponatinib for intolerant patients.
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29845876 |
2018 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation.
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28969556 |
2018 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
In addition, this agent was equally effective in inhibiting the Wnt/β‑catenin signaling in wild‑type and T315I BCR‑ABL CML cells.
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28990077 |
2017 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Here we further report that (i) PtPT induces apoptosis in Bcr-Abl wild-type and Bcr-Abl-T315I mutation cells including the primary mononuclear cells from CML patients clinically resistant to IM, as well as inhibits the growth of IM-resistant Bcr-Abl-T315I xenografts in vivo; (ii) PtPT downregulates Bcr-Abl level through restraining Bcr-Abl transcription, and decreasing Bcr-Abl protein mediated by DUBs inhibition-induced caspase activation; (iii) UPS inhibition is required for PtPT-induced caspase activation and cell apoptosis.
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28682311 |
2017 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
SHC004-221A1, a novel tyrosine kinase, potently inhibits T315I mutant BCR-ABL in chronic myeloid leukemia.
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28595903 |
2017 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
In the United States, ponatinib has received accelerated approval for adults with T315I-positive chronic myeloid leukemia (CML) or T315I (gatekeeper mutation)-positive, Philadelphia chromosome-positive, acute lymphoblastic leukemia (Ph + ALL), and patients with CML or Ph + ALL for whom no other TKI therapy is indicated.
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28184964 |
2017 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
We have now demonstrated that protein expression of human estrogen receptor alpha 36 (ERα36), an alternative splicing variant of human estrogen receptor alpha 66 (ERα66), is highly increased in TKI-insensitive CD34+ chronic myeloid leukemia (CML) cells and BCR-ABL-T315I mutant cells, and is abnormally localized in plasma membrane and cytoplasm.
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28599273 |
2017 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
ARDAP derivative <b>10</b> inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation.
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28523104 |
2017 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Ultra-deep sequencing leads to earlier and more sensitive detection of the tyrosine kinase inhibitor resistance mutation T315I in chronic myeloid leukemia.
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27102501 |
2016 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML.
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27329306 |
2016 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
In a xenograft model, PD0332991, but not imatinib, suppressed dissemination of Ph(+) ALL having the T315I mutation and prolonged survival, demonstrating that this reagent would be a new therapeutic modality for relapsed CML-LC and Ph(+) ALL patients after treatment with tyrosine kinase inhibitors.
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26637365 |
2016 |
rs121913459
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0.800 |
GeneticVariation |
BEFREE |
Taken together, our data demonstrate that the lower growth ability of KBM5-T315I CML cells might be related to the decreased expression of glycolysis-related genes and ROS levels, and this will be used to identify therapeutic targets for imatinib resistance in CML.
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26854822 |
2016 |