|
Leukemia, Myelocytic, Acute
|
0.700 |
CausalMutation
|
disease |
CGI |
|
|
|
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
<b/> AG-221 or enasidenib is a first-in-class selective inhibitor of mutated isocitrate dehydrogenase 2 (IDH2) with early demonstrated clinical efficacy in acute myeloid leukemia as a single agent, yet with persistence of mutant <i>IDH2</i> clones.
|
28461409 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Acute myeloid leukemia (AML) cells harboring mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) produce the oncometabolite 2-hydroxyglutarate (2HG).
|
30422308 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Acute myeloid leukemia with isolated del(5q) was less likely therapy-related (p = 0.037), more likely to have IDH1/IDH2 mutations (p = 0.009), and less likely to have TP53 mutations (p = 0.005) when compared to acute myeloid leukemia with complex karyotype including del(5q).
|
31685963 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
IDH2 mutations included R140Q (n=3; one post-PMF AML, one post-PV AML and one PMF) and a novel R140W (n=1; mutation found in both chronic- and blast-phase samples).
|
20410924 |
2010 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
IDH mutations may be a novel genetic marker in cytogenetically normal AML and may cooperate in leukemogenesis.
|
22494415 |
2012 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
IDH2 inhibition in AML: Finally progress?
|
26590767 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
A CpG island methylator phenotype in acute myeloid leukemia independent of IDH mutations and associated with a favorable outcome.
|
28074068 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
A recent research of cancer has indicated that the mutant of isocitrate dehydrogenase 1 and 2 (IDH1 and 2) genes will induce various cancers, including chondrosarcoma, cholangiocarcinomas, and acute myelogenous leukemia due to the effect of point mutations in the active-site arginine residues of isocitrate dehydrogenase (IDH), such as IDH1/R132, IDH2/R140, and IDH2/R172.
|
24995286 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Acquired somatic mutations of IDH1 and IDH2 have recently been reported in some types of brain tumors and a small proportion of acute myeloid leukemia (AML) cases.
|
22397365 |
2012 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
Additionally, targeted therapies are now becoming available for patients with mutations in FMS-like tyrosine kinase 3 (FLT3) or isocitrate dehydrogenase 2 (IDH2), ushering in an era of personalized medicine in the treatment of AML.
|
29283906 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
AG-221, a small-molecule inhibitor of mutant IDH2, is being explored in a phase I clinical trial for the treatment of AML, other myeloid malignancies, solid tumors, and gliomas.
|
26553750 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
All subjects with TP53 mutations (n = 21 out of 21 patients) and IDH1 and IDH2 (n = 15 out of 15 patients) mutations eventually developed AML in our study.
|
29988143 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Although no new drug has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration "breakthrough" designation granted to venetoclax, and promising agents such as the IDH inhibitors AG-221 and AG-120, the smoothened inhibitor glasdegib and the histone deacetylase inhibitor pracinostat.
|
28286924 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated.
|
21079611 |
2011 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Although the first reports have also already emerged describing acquired resistance for these mutant IDH inhibitors, combination treatment might overcome this problem, which could drastically change the treatment landscape of AML over the next few years.
|
30643428 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Among 39 patients with newly diagnosed mutant-IDH2 AML who received enasidenib monotherapy in this phase I/II trial, median age was 77 years (range 58-87) and 23 patients (59%) had had an antecedent hematologic disorder.
|
30967620 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
As the genetic landscape of AML has been mapped, other attractive targets for therapy have been discovered, including C-KIT, IDH1 and IDH2, NPM1, and MEK.
|
26111466 |
2015 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies.
|
29439493 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Biochemical, Epigenetic, and Metabolic Approaches to Target IDH Mutations in Acute Myeloid Leukemia.
|
26111463 |
2015 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib.
|
30013198 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
Comparison of HRM to Sanger sequencing on 146 AML bone marrow samples for validation showed near-perfect concordance for all positive and negative results for IDH1 (98%) and IDH2 (94%).
|
21889610 |
2011 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
Detection of Dual IDH1 and IDH2 Mutations by Targeted Next-Generation Sequencing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.
|
26331834 |
2015 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies.
|
24699305 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Due to the fact that mutations in IDH1 and IDH2 are acquired early during AML clonal evolution as well as because these mutations tend to remain stable during AML progression, the pharmaceutical industry has prompted the development of specific mutant IDH enzyme inhibitors.
|
29090344 |
2017 |