|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Altogether, we show that TCL1 mRNA expression may predict clinical outcome in CLL and that the IGHV3-21 subset, regardless of mutational status, displays high TCL1 expression.
|
19889012 |
2010 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We show enhanced CLL disease progression in IRF4-deficient Tcl-1 tg mice, associated with a severe downregulation of genes involved in T-cell activation, including genes involved in antigen processing/presentation and T-cell costimulation, which massively reduced T-cell subset skewing and exhaustion.
|
31537531 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
We have shown in a recent paper that miR-34a is severely increased in the TCL1-mouse model of CLL.
|
20581456 |
2010 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, our results uncover that the genetic complexity, pathway dependence and clonal dynamics in mouse CLL are in relevant agreement to human CLL, and they are important to consider in future research using the TCL1 mouse for studying CLL.
|
30262843 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here, we utilized the Eµ-TCL1 mouse model of CLL as well as blood and lymph node samples of CLL patients to investigate the existence of anti-tumoral immune responses in CLL, and to characterize involved immune cell populations.
|
30267008 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
To determine whether pathologic usurpation of this pathway plays a role in B-cell leukemogenesis, we examined the expression of Wnt/Fzd pathway genes in the Emu-TCL1 mouse model of chronic lymphocytic leukemia.
|
19179304 |
2009 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using the Eµ-TCL1 adoptive transfer model of CLL, we show that disease development induces the accumulation of activated and highly immunosuppressive Tregs.
|
30573773 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Molecular details of how activation of TCL1, a critical oncogene in aggressive CLL, results in the initiation of this malignancy were clarified.
|
20863894 |
2010 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings demonstrate that the microenvironment has a proactive role in the regulation of the known signaling enhancer and pro-survival molecule TCL1 in CLL.
|
22460735 |
2012 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
On the other hand, in CLL cases that use unmutated immunoglobulin heavy-chain variable-region genes (IgV(H)) or have high-level expression of the 70-kD zeta-associated protein (ZAP-70) have high levels of TCL1 due to low-level expression of miR-29 and miR-181, which directly target this oncogene.
|
17707831 |
2007 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, PKCbeta-deleted TCL1 transgenic mice did not develop a CLL disease, suggesting a role of PKCbeta in the establishment of the malignant clone.
|
19168795 |
2009 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here, we found that genetic inactivation of p110δ (p110δD910A/D910A) in the Eμ-TCL1 murine chronic lymphocytic leukemia (CLL) model impaired B cell receptor signaling and B cell migration, and significantly delayed leukemia pathogenesis.
|
30457982 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
With development of leukemia, Emu-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients.
|
19332800 |
2009 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
TCL1 expression patterns in CLL are complex and highly dynamic and appear to reflect both the histogenetic subtypes of the disease and the growth parameters of individual tumors.
|
16341048 |
2006 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the well-established TCL1 transgenic mouse model for high-risk CLL, actinomycin D treatment was more effective in reducing tumor load than fludarabine, with no evidence of resistance after three treatment cycles and an overall survival increase of over 300%.
|
22743622 |
2012 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, IGF1R inhibition effectively limited CLL development in Eμ-TCL1 transgenic mice and of primary human CLL xenografts.
|
23863897 |
2013 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Overall, these studies suggest that the TCL-1 transgenic leukemia mouse model has similar clinical and therapeutic response properties to human CLL and may therefore serve as a useful in vivo tool to screen new drugs for subsequent development in CLL.
|
16670263 |
2006 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Inhibition of BTK kinase activity through either targeted genetic inactivation or ibrutinib in the TCL1 mouse significantly delays the development of CLL, demonstrating that BTK is a critical kinase for CLL development and expansion and thus an important target of ibrutinib.
|
24311722 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181.
|
17178851 |
2006 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings provide an animal model for CLL, the most common human leukemia, and demonstrate that deregulation of the Tcl1 pathway plays a crucial role in CLL pathogenesis.
|
12011454 |
2002 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
ROR1 is a receptor for Wnt5a that may complex with TCL1, a coactivator of AKT that is able to promote development of CLL.
|
27815263 |
2016 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Finally, we observed a fludarabine potentiation by SCH900776 in a T-cell leukemia 1 (TCL1)-driven mouse model of CLL.
|
27556692 |
2016 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the Eµ-TCL1 adoptive transfer mouse model of CLL, ND2158 delayed tumor progression and modulated the activity of myeloid and T cells.
|
31197259 |
2020 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Herein, we used a CLL mouse model (Eμ-TCL1) harboring one of the most common TP53 hot-spot mutations observed in CLL (p53(R172H), corresponding to p53(R175H) in humans) to evaluate its impact on disease progression, survival, response to therapy and loss of the remaining wild-type Trp53 allele following ibrutinib treatment.
|
27284738 |
2016 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings revealed biochemical and immunological similarities between Tcl1-driven B-CLL in mice and human B-CLL.
|
20357824 |
2010 |