|
Leukemia, Myelocytic, Acute
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
It perturbed Pim-kinase-mediated AML cell signaling, such as attenuation of Stat5 or MDM2 phosphorylation, and synergized with DNR to induce AML cell death.
|
30679386 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
We herein briefly discuss currently approved therapies in AML and review the clinical data for RG7388 (idasanutlin) and MDM2 inhibition as novel treatment strategies in AML.
|
31289443 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We speculate that these alterations in the Mdm2-p53 pathway contribute to the development of AML in patients with t (8,21) and somatically mutated DHX15.
|
31691804 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
While a number of inhibitors of the MDM2-p53 interaction have progressed to clinical testing as treatments for a variety of hematologic and solid tumor cancers, the results thus far have been mixed, with perhaps the strongest responses observed in relapsed/refractory acute myeloid leukemia (AML).
|
30575392 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Targeting of p53-MDM2 interaction to reactivate p53 function is therefore an attractive therapeutic approach for AML.
|
31653912 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here, we assessed the MCL1-antagonist S63845, the MDM2-inhibitor HDM201, and the MEK1/2-inhibitor trametinib as single agents and in combination in a variety of AML cell lines and mononuclear cells isolated from patients with hematological malignancies centered on myeloid leukemia, some lymphatic leukemia, as well as some lymphomas, for their ability to induce apoptosis and cell death.
|
31718075 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We have examined the association of N MDM2 -309T>G polymorphism in 73 cases diagnosed with AML and 80 healthy controls by tetra-primer amplification refractory mutation system (ARMS) PCR assay.
|
31653152 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
MTF2 represses MDM2 in hematopoietic cells and its loss in AML results in chemoresistance.
|
30115703 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here we assessed the MDM2 antagonist idasanutlin and the MEK1 inhibitor cobimetinib as single agents and in combination in a variety of AML cell lines and primary AML blast cells for their ability to induce apoptosis and cell death.
|
29857559 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Here we report the design of a fluorescent lanthanide oxyfluoride nanoparticle (LONp)-based multifunctional peptide drug delivery system for potential treatment of acute myeloid leukemia (AML) that commonly harbors wild type p53, high levels of MDM2 and/or MDMX, and an overexpressed cell surface receptor, CD33.
|
29571049 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
First, by comparing sensitivity to MDM2 inhibition with basal mRNA expression profiles in 240 cancer cell lines, a 175-gene signature was defined and validated in patient-derived tumor xenograft models and <i>ex vivo</i> human acute myeloid leukemia (AML) cells.
|
29490944 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study, we investigated the utility of MDM2 and p16 along with HMB45 and Melan-A immunohistochemical analysis in distinguishing AML from WDL/DDLS or lipoma.
|
29432785 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The tumor suppressor p53 is often inactivated via its interaction with endogenous inhibitors mouse double minute 4 homolog (MDM4 or MDMX) or mouse double minute 2 homolog (MDM2), which are frequently overexpressed in patients with acute myeloid leukemia (AML) and other cancers.
|
29643228 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
We examined a large AML cohort using proteomics, mutational profiling and network analyses, and showed that (1) p53 stabilization is universal in mutant TP53 samples, it is frequent in samples with wild-type TP53, and in both cases portends an equally dismal prognosis; (2) the p53 negative regulator Mdm2 is frequently overexpressed in samples retaining wild-type TP53 alleles, coupled with absence of p21 expression and dismal prognosis similar to that of cases with p53 stabilization; (3) AML samples display unique patterns of p53 pathway protein expression, which segregate prognostic groups with distinct cure rates; (4) such patterns of protein activation unveil potential AML vulnerabilities that can be therapeutically exploited.
|
27885271 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML.
|
27256803 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Using reverse-phase protein array technology, we profiled 53 key protein molecules in 11 signaling pathways in 20 primary acute myeloid leukemia samples and two cell lines, aiming to understand stroma-mediated signaling modulation in response to the targeted agents temsirolimus (MTOR), ABT737 (BCL2/BCL-XL), and Nutlin-3a (MDM2), and to identify the effective combination therapy targeting acute myeloid leukemia in the context of the leukemia microenvironment.
|
28659338 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results indicate that p53-independent upregulation of MDM2 by increasing selected clones may lead to oncogenesis in AML and that MDM2-modulating genes are novel potential targets for AML treatment.
|
27524244 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.
|
27353420 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification.
|
27369456 |
2016 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Role of the MDM2 promoter polymorphism (-309T>G) in acute myeloid leukemia development.
|
25854351 |
2015 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
TP53 mutations and MDM2(SNP309) identify subgroups of AML patients with impaired outcome.
|
25156865 |
2015 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The small molecule inhibitor of the MDM2/p53 interaction Nutlin-3 is a promising anti-cancer agent, which exhibits activity against a variety of cancers, including acute myeloid leukemia (AML).
|
23192887 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
High levels of Mdm4 do not block function of Mdm2 inhibitors in AML.
|
24659749 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
The small-molecule MDM2 antagonist nutlin-3 has proved to be an effective p53 activating therapeutic compound in several preclinical cancer models, including acute myeloid leukemia (AML).
|
24885082 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk.
|
23167335 |
2012 |