|
leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Consistent with this hypothesis, mice transplanted with T-cells co-expressing NOTCH1 and NRARP develop leukemia later than mice transplanted with T-NOTCH1 cells.
|
31586130 |
2020 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using loss-of-function approaches, we show that Il7r-deficient, but not wild-type, mouse hematopoietic progenitors transduced with constitutively active Notch1 failed to generate leukemia upon transplantation into immunodeficient mice, thus providing formal evidence that IL-7R function is essential for Notch1-induced T-cell leukemogenesis.
|
31530562 |
2019 |
|
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 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Hepatic leukemia-associated macrophages exhibit a pro-inflammatory phenotype in Notch1-induced acute T cell leukemia.
|
29030004 |
2018 |
|
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 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Chemotactic Cues for NOTCH1-Dependent Leukemia.
|
29666622 |
2018 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Characterization of peritoneal leukemia-associated macrophages in Notch1-induced mouse T cell acute lymphoblastic leukemia.
|
27888718 |
2017 |
|
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 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature.
|
28716817 |
2017 |
|
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 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development.
|
26931577 |
2016 |
|
leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Finally, we identify perhexiline, a small-molecule inhibitor of mitochondrial carnitine palmitoyltransferase-1, as a HES1-signature antagonist drug with robust antileukemic activity against NOTCH1-induced leukemias in vitro and in vivo.
|
25784680 |
2015 |
|
leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Restoring endogenous Ikaros expression in established T-ALL in vivo acutely represses Notch1 and its oncogenic target genes including Myc, and in multiple primary leukemias causes disease regression.
|
25655195 |
2015 |
|
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 |
|
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 |
|
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 |
|
leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Consistently, these leukaemias show lower frequencies of prototypical T-ALL lesions such as CDKN2A/B deletions and activating mutations in NOTCH1 and show a higher prevalence of mutations typically associated with the pathogenesis of acute myeloid leukaemias (AMLs).
|
23695450 |
2013 |
|
leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The IG-BMI1 translocations were not associated with any particular molecular subtype of CLL and the leukemias were negative for common mutations of NOTCH1 and TP53, known to increase a risk of progression and transformation in CLL.
|
23873701 |
2013 |
|
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 |
|
leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mutagenesis screens previously implicated ZMIZ1 as a possible NOTCH1 collaborator in leukemia.
|
23161489 |
2013 |
|
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 |
|
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 |
|
leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Echinomycin suppresses leukaemia cell growth in association with reduced NOTCH1 expression.
|
23898065 |
2013 |
|
leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia.
|
22225590 |
2012 |
|
leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We have investigated the possible regulative role of Notch1 on the expression and function of chemokine receptors CCR5, CCR9 and CXCR4 that play a role in determining blast malignant properties and localization of extramedullary infiltrations in leukaemia.
|
21984373 |
2012 |