|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
IDH1 and IDH2 mutations in patients with acute myeloid leukemia: Suitable targets for minimal residual disease monitoring?
|
30176240 |
2018 |
|
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 |
Together, our studies suggest combined targeting of signaling and epigenetic pathways can increase therapeutic response in AML.<b>Significance:</b> AMLs with mutations in <i>TET2</i> or <i>IDH2</i> are sensitive to epigenetic therapy through inhibition of DNA methyltransferase activity by 5-azacytidine or inhibition of mutant IDH2 through AG-221.
|
28193779 |
2017 |
|
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 |
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has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration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 |
Using the IDH2 R140Q mutation as a model, we present a new effective methodology here using the RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to reproduce or remove AML-associated mutations in or from human leukemic cells, respectively, via introduction of a DNA template at the endogenous gene locus via homologous recombination.
|
28325290 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
The measurement of D-2-hydroxyglutarate in peripheral blood may be used as a biomarker for screening and follow-up of patients with IDH-mutated acute myeloid leukemia.
|
28735490 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
CTD_human |
Dynamics of clonal evolution in myelodysplastic syndromes.
|
27992414 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia.
|
29064021 |
2017 |
|
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 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
This article summarizes the milestones in the development of enasidenib leading to this first global approval in the USA for the treatment of adults with relapsed or refractory IDH2-mutated AML.
|
28879540 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Nanofluidic Allele-Specific Digital PCR Method for Quantifying IDH1 and IDH2 Mutation Burden in Acute Myeloid Leukemia.
|
28735491 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
This review surveys the use of tyrosine kinase inhibitors to treat patients with mutant FLT3 AML, mutant KIT AML, as well as IDH inhibitors and explores some questions regarding their integration into the treatment armamentarium for AML.
|
29156201 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS).
|
27721426 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
IDH2 inhibition in AML: Finally progress?
|
26590767 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
|
26619011 |
2016 |
|
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 |
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
|
27005468 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
Biomarker
|
disease |
BEFREE |
In the hematopoietic system, mutations in IDH1 at arginine (R) 132 and in IDH2 at R140 and R172 are commonly observed in acute myeloid leukemia, and elevated 2HG is observed in cells and serum.
|
27956631 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
They then show that elevated levels of 2-HG are correlated with mutations in IDH1 and IDH2 in AML patient samples (Figure 5).
|
26943899 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
More importantly, we validated the R-2HG-activated gene signature in the primary bone marrow stromal cells isolated from IDH-mutated AML patients.
|
27577048 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
CLINVAR |
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
|
26619011 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We thus conclude that pretreatment D2HG serum levels may yield prognostic information in patients with IDH1-mutated, but not in IDH2-mutated AML, possibly due to different subcellular localizations of IDH1 and IDH2.
|
26582645 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In other malignancies, such as acute myeloid leukemia, presence of IDH mutation is associated with elevated 2-HG levels in serum or urine compartments.
|
26834160 |
2016 |