|
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 |
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 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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
Then, they analyzed the levels of MDM-2 protein expression and correlated it with prognosis in an expanded population of 79 adults with AML by immunoblot analysis and solid-phase radioimmunoassay.
|
11064355 |
2000 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These results suggest that GM-CSF-independent growth of AML cells is associated with overexpression of MDM2 protein and related modulation of p53 expression.
|
9680365 |
1998 |
|
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 |
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 |