|
leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Although many imatinib-resistant mutations respond well to second-generation TKIs, the threonine-to-isoleucine mutation at codon 315 of the breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene protein fusion Bcr-Abl (T315I) is insensitive to all currently available TKIs.
|
20564073 |
2010 |
|
B Acute Lymphoblastic Leukemia with t(9;22)(q34.1;q11.2); BCR-ABL1
|
|
0.100 |
GeneticVariation
|
BEFREE |
We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.
|
20388735 |
2010 |
|
leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Although strategies to overcome resistance-mediated T315I mutation may improve the survival of BCR-ABL-positive leukemia patients, there is little information on cell-based studies.
|
20471447 |
2010 |
|
B Acute Lymphoblastic Leukemia with t(9;22)(q34.1;q11.2); BCR-ABL1
|
|
0.100 |
GeneticVariation
|
BEFREE |
Establishment of a new Philadelphia chromosome-positive acute lymphoblastic leukemia cell line (SK-9) with T315I mutation.
|
20471447 |
2010 |
|
Childhood Leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Although many imatinib-resistant mutations respond well to second-generation TKIs, the threonine-to-isoleucine mutation at codon 315 of the breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene protein fusion Bcr-Abl (T315I) is insensitive to all currently available TKIs.
|
20564073 |
2010 |
|
Childhood Leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Although strategies to overcome resistance-mediated T315I mutation may improve the survival of BCR-ABL-positive leukemia patients, there is little information on cell-based studies.
|
20471447 |
2010 |
|
leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukemia patients.
|
19541823 |
2009 |
|
leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
Some emerging aurora kinase inhibitors, such as VX-680, PHA-739358, MK-0457 and AS703569, and Smo1 and Hedgehog (Hh) inhibitors promise clinical efficacy against the Bcr-Ab T315I mutant form and leukaemia stem cells, respectively.
|
19959093 |
2009 |
|
Childhood Leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukemia patients.
|
19541823 |
2009 |
|
B Acute Lymphoblastic Leukemia with t(9;22)(q34.1;q11.2); BCR-ABL1
|
|
0.100 |
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 |
|
B Acute Lymphoblastic Leukemia with t(9;22)(q34.1;q11.2); BCR-ABL1
|
|
0.100 |
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 |
|
leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
More importantly, ON012380 was found to induce apoptosis of all of the known imatinib-resistant mutants at concentrations of <10 nM concentration in vitro and cause regression of leukemias induced by i.v. injection of 32Dcl3 cells expressing the imatinib-resistant BCR-ABL isoform T315I.Daily i.v. dosing for up to 3 weeks with a >100 mg/kg concentration of this agent is well tolerated in rodents, without any hematotoxicity.
|
15677719 |
2005 |
|
leukemia
|
|
0.100 |
GeneticVariation
|
BEFREE |
The resistance to the tyrosine kinase inhibitor imatinib in BCR/ABL-positive leukemias is mostly associated with mutations in the kinase domain of BCR/ABL, which include the most prevalent mutations E255K and T315I.
|
15194504 |
2004 |
|
Acute lymphoblastic leukemia with lymphomatous features
|
|
0.700 |
GeneticVariation
|
CLINVAR |
Prospective enterprise-level molecular genotyping of a cohort of cancer patients.
|
25157968 |
2014 |
|
Acute lymphoblastic leukemia with lymphomatous features
|
|
0.700 |
GeneticVariation
|
CLINVAR |
MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia.
|
22772060 |
2013 |
|
Acute lymphoblastic leukemia with lymphomatous features
|
|
0.700 |
GeneticVariation
|
CLINVAR |
Ph(+) acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation.
|
11861307 |
2002 |
|
LEUKEMIA, PHILADELPHIA CHROMOSOME-POSITIVE, RESISTANT TO IMATINIB
|
|
0.700 |
CausalMutation
|
CLINVAR |
|
|
|
|
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 |
Preclinical development of a novel BCR-ABL T315I inhibitor against chronic myeloid leukemia.
|
31837444 |
2020 |
|
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 |
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.
|
30711891 |
2019 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
31034603 |
2019 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
31673329 |
2019 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
31785158 |
2019 |
|
Myeloid Leukemia, Chronic
|
|
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.
|
31761618 |
2019 |