|
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 |
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 |
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 |
GeneticVariation
|
disease |
BEFREE |
These results suggest that the MDM2 SNP309 homozygous GG genotype may be a genetic susceptibility factor in the pathogenesis of AML.
|
19423162 |
2009 |
|
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 |
GeneticVariation
|
disease |
BEFREE |
Of the 10 lines without overexpression of the MDM2 gene, six (including the AML line) did not express p53, and four expressed mutant p53 with single point mutations in exons 7 and 8.
|
7888679 |
1995 |
|
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 |
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 |
Biomarker
|
disease |
BEFREE |
Activation of p53 by murine double minute (MDM2) antagonist nutlin-3a or inhibition of X-linked inhibitor of apoptosis (XIAP) induces apoptosis in acute myeloid leukemia (AML) cells.
|
19897582 |
2010 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
We report that treatment with MI-63, a novel inhibitor of MDM2, activates p53 signaling to induce apoptosis in AML cell lines and primary samples.
|
20423286 |
2010 |
|
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 |
|
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 |
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 |
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 |
We investigated the interaction of FLT3 and p53 pathways after their simultaneous blockade using the selective FLT3 inhibitor FI-700 and the MDM2 inhibitor Nutlin-3 in AML.
|
19946262 |
2010 |
|
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 |
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 |
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 |
Our findings provide the molecular rationale for concomitant targeting of Aurora kinases and Mdm2 in AML where TP53 mutations are rare and downstream p53 signaling is mostly intact.
|
18633130 |
2008 |
|
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 |
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 |
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 |
Biomarker
|
disease |
BEFREE |
Finally, analysis of very sensitive AML cases uncovered a strong and significant association with mutated Flt3 status (Flt3-ITD), which for the first time identified a clinically high-risk group of AML that may particularly benefit from MDM2 inhibitor treatment.
|
20404136 |
2010 |