|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Acute myeloid leukemia (AML) cells are characterized by non-mutated TP53, high levels of Hdm2, and frequent mutation of the Flt3 receptor tyrosine kinase.
|
17498302 |
2007 |
|
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 |
All MDM2+ AMLs evaluated by FISH (n=4) were negative for MDM2 amplification.
|
27369456 |
2016 |
|
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 |
|
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 |
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 |
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 |
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 |
High levels of Mdm4 do not block function of Mdm2 inhibitors in AML.
|
24659749 |
2014 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Immunohistochemical staining detected a weak accumulation of the MDM-2 protein in AML patients of FAB classification M4 and M5.
|
8898928 |
1996 |
|
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 |
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 |
MTF2 represses MDM2 in hematopoietic cells and its loss in AML results in chemoresistance.
|
30115703 |
2018 |
|
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 |
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 |
Our results suggest the concomitant targeting of MDM2-p53 and HDAC inhibition, may be an effective therapeutic strategy for the treatment of AML.
|
22064349 |
2012 |
|
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 |
AlteredExpression
|
disease |
BEFREE |
Since p14(ARF) has been demonstrated to inhibit p53 degradation by binding to MDM2, repression of p14(ARF) expression in t(8;21)AML may facilitate the degradation of p53 by MDM2.
|
16162359 |
2006 |
|
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 |
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 |
The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML.
|
18548093 |
2008 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The purpose of this study was to define P53 gene mutations, to detect MDM2 gene amplification and to estimate mRNA expression of P53, MDM2, BCL2 and BAX genes in patients with ALL and AML.
|
16059649 |
2005 |
|
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 |
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 |