|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
The viral oncogene Np9 acts as a critical molecular switch for co-activating β-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells.
|
23307033 |
2013 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells.
|
27872496 |
2017 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL.
|
21670468 |
2011 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1(+)CD19(+) precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro.
|
21622646 |
2011 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
In murine models of T-ALL, Notch-1 activation can both directly initiate leukemia and cooperate secondarily to other primary events.
|
18056171 |
2007 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Chemotactic Cues for NOTCH1-Dependent Leukemia.
|
29666622 |
2018 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
To identify Notch1 target genes in leukemia, we developed mouse T-cell leukemic lines that express intracellular Notch1 in a doxycycline-dependent manner.
|
16954387 |
2006 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL.
|
23908464 |
2013 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
We sequenced the heterodimerization domain and the PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors harbor activating mutations in Notch1.
|
16166587 |
2006 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Leukemia initiating cells (LIC) contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches.
|
22768113 |
2012 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Hepatic leukemia-associated macrophages exhibit a pro-inflammatory phenotype in Notch1-induced acute T cell leukemia.
|
29030004 |
2018 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model.
|
19652197 |
2009 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In contrast to the strict and differential use of ADAM10 and ADAM17 in normal and dysregulated signaling, respectively, both proteases participated in signaling intrinsic to N1 mutations associated with leukemia.
|
19704010 |
2009 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations.
|
22491738 |
2012 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Several genetic alterations are intuitively "druggable" with existing agents, for example, kinase-activating lesions in high-risk B-cell ALL, NOTCH1 in both leukemia and lymphoma, and BRAF in hairy cell leukemia.
|
24041576 |
2013 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Together these results identify N-Me as a long-range oncogenic enhancer implicated directly in the pathogenesis of human leukemia and highlight the importance of the NOTCH1-MYC regulatory axis in T cell transformation and as a therapeutic target in T-ALL.
|
25194570 |
2014 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We found activating mutations in NOTCH1 in a single M0 primary AML sample, in three (ML1, ML2 and CTV-1) out of 23 AML cell lines and in the diagnostic (myeloid) and relapsed (T-lymphoid) clones in a patient with lineage switch leukemia.
|
17008890 |
2006 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
We demonstrate that ubiquitin-specific protease 7 (USP7) interacts with NOTCH1 and controls leukemia growth by stabilizing the levels of NOTCH1 and JMJD3 histone demethylase.
|
30224337 |
2019 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes.
|
16738328 |
2006 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
NOTCH1 mRNA and surface protein expression levels were independent of the NOTCH1 gene mutational status, consistent with the requirement for NOTCH1 signaling in this leukemia.
|
24170027 |
2014 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Together, these data identify a mechanism for enhancing the oncogenic potential of weak Notch1 mutants in leukemia models, and they reveal the MAFB-ETS2 transcriptional axis as a potential therapeutic target in T-ALL.
|
29138297 |
2017 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
The role of the PTEN/AKT Pathway in NOTCH1-induced leukemia.
|
18414037 |
2008 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
These proof-of-concept studies support the further optimization of this first-in-class NOTCH1 inhibitor with dual selectivity: leukemia over normal cells and NOTCH1 mutants over wild-type receptors.
|
29158376 |
2018 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Although these mutations are not detected at the pre-leukemia stage, incremental up-regulation of NOTCH1 surface expression is observed at the pre-leukemia and leukemia stages.
|
23673656 |
2013 |
|
Childhood Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These markers included various first- and second-hit genetic alterations (TCRD-LMO2 breakpoint regions, n = 2; TAL1 deletions, n = 3; Notch1 mutations, n = 1) and nononcogenic T-cell receptor rearrangements (n = 13) that were derived from leukemias of 16 children who were 1.5 to 11.2 years old at diagnosis of leukemia.
|
17557895 |
2007 |