|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
In chronic myelogenous leukemia (CML)--chronic phase (CP), 5 had P-loop mutations and 3 had T315I mutations.
|
21239056 |
2011 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
In the present study, an allele-specific oligonucleotide reverse transcriptase polymerase chain reaction assay was used to detect T315I mutation in a cohort of 60 imatinib-resistant CML patients.
|
23540562 |
2013 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
The aim of this study was to evaluate proliferation inhibition and apoptosis induction by down-regulating PPP2R5C gene expression in the imatinib-sensitive and imatinib-resistant CML cell lines K562, K562R (imatinib resistant without an Abl gene mutation), 32D-Bcr-Abl WT (imatinib-sensitive murine CML cell line with a wild type Abl gene) and 32D-Bcr-Abl T315I (imatinib resistant with a T315I Abl gene mutation) and primary cells from CML patients by RNA interference.
|
24004697 |
2013 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
We conclude that (a) amino acid substitutions at seven residues (M244V, G250E, Y253F/H, E255K/V, T315I, M351T, and F359V) account for 85% of all resistance-associated mutations; (b) the search for mutations is important both in case of imatinib failure and in case of loss of response at the hematologic or cytogenetic level; (c) advanced-phase chronic myeloid leukemia and Ph+ ALL patients have a higher likelihood of developing imatinib-resistant mutations; and (d) the presence of either P-loop or T315I mutations in imatinib-treated patients should warn the clinician to reconsider the therapeutic strategy.
|
17189410 |
2006 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
26854822 |
2016 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
26637365 |
2016 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
31101753 |
2020 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
28184964 |
2017 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Allogeneic transplantation remains an important therapeutic option for CML-CP harboring the T315I mutation, patients who fail 2nd generation TKIs, and for all patients in advanced phase disease.
|
23090888 |
2012 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
28682311 |
2017 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Ponatinib (AP24534) is currently the only approved CML drug that is active against the ABL1(T315I) mutation.
|
29608815 |
2018 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
To our knowledge, this is the second case of a T315I-bearing chronic myeloid leukemia patient displaying satisfactory response to the combination therapy of dasatinib and IFN-α.
|
27347777 |
2016 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
The observation of responses in 3 patients with T315I phenotype-refractory CML or Ph-positive ALL, at doses of MK-0457 associated with no significant extramedullary toxicity, is very encouraging.
|
16990603 |
2007 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
30555164 |
2019 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
T315I-mutated Bcr-Abl in chronic myeloid leukemia and imatinib: insights from a computational study.
|
16093432 |
2005 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Although, we continued to monitor bcr-abl transcripts in 14 CML patients (13 chronic phases and 1 accelerated phase) for up to 12 months, there were no patients who were apparently resistant to imatinib due to the T315I mutation.
|
19343480 |
2009 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
29845876 |
2018 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Identification of new agents capable of effectively killing CML cells with T315I mutation would have important therapeutic implications in Gleevec-resistant CML.
|
18385754 |
2008 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Inhibition of Aurora A induced apoptosis of CML cells with or without T315I BCR-ABL mutation and suppressed CML cell growth.
|
22116466 |
2012 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations.
|
27214026 |
2016 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
28599273 |
2017 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
28990077 |
2017 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Despite the great success in using tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML), the frequent development of multi-drug resistance, particularly the T315I mutation of BCR-ABL, remains a challenging issue.
|
25900240 |
2015 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation.
|
19843886 |
2009 |
|
Myeloid Leukemia, Chronic
|
|
0.800 |
GeneticVariation
|
BEFREE |
Treatment with these inhibitors results in potent suppression of chronic myeloid leukemia leukemic precursors and Ph(+) acute lymphoblastic leukemia cells, including cells expressing the T315I-BCR-ABL mutation.
|
22021366 |
2011 |