Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Here, we summarize the present knowledge of CLL metabolism, as well as the metabolic influence of Myc, ATM and p53 on CLL lymphocytes.
|
30771875 |
2019 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, CLL patients with several chromosomal gains exhibit high genetic instability, with mutations in CLL driver genes and high-risk genetic alterations involving ATM and/or TP53 genes.
|
30807786 |
2019 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p < 0.05).
|
29720177 |
2018 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Overall, 69 somatic mutations in 29 CLL driver genes were detected among 45 subjects (46%), with the most frequently mutated genes being TP53 (8·2%), NOTCH1 (8·2%) and ATM (5·1%).
|
29687880 |
2018 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
We show that non-coding mutations in ATM may negatively impact on ATM expression and find non-coding and regulatory region mutations in TCL1A, and in IgHV<sup>unmut</sup> CLL in IKZF3, SAMHD1,PAX5 and BIRC3.
|
28584254 |
2018 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Lastly, we highlight the results of early clinical data on novel compounds targeting defects in the DNA damage response of CLL with a particular focus on deleterious ATM mutations.
|
29702521 |
2018 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Our results suggest the identification of ATM mutations in CLL patients with 11q deletion at diagnosis is clinically relevant and predicts disease progression, poor response to the treatment, and reduced OS independent of other molecular prognostic factors.
|
27499002 |
2017 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
To test this hypothesis, we studied the effect of USP7 inhibition in chronic lymphocytic leukemia (CLL) where the ataxia telangiectasia mutated (ATM)-p53 pathway is inactivated with relatively high frequency, leading to treatment resistance and poor clinical outcome.
|
28495793 |
2017 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04).
|
27678008 |
2017 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Thus, we generate two aggressive CLL models and provide a preclinical rational for the use of PARP inhibitors in ATM-affected human CLL.ATM and TP53 mutations are associated with poor prognosis in chronic lymphocytic leukaemia (CLL).
|
28751718 |
2017 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
This was confirmed in vivo using primary xenograft models of TP53- or ATM-defective CLL, where treatment with AZD6738 resulted in decreased tumor load and reduction in the proportion of CLL cells with such defects.
|
26563132 |
2016 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia.
|
26837699 |
2016 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2).
|
27588518 |
2016 |
Chronic Lymphocytic Leukemia
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Incubation of CLL-exosomes, derived either from cell culture supernatants or from patient plasma, with human stromal cells shows that they are readily taken up into endosomes, and induce expression of genes such as c-fos and ATM as well as enhance proliferation of recipient HS-5 cells.
|
26509439 |
2015 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The MEC-1 and GRANTA-519 cells can be especially recommended for in vivo study of p53-mutated chronic lymphocytic leukemia and ATM-mutated mantle cell lymphoma, respectively.
|
25827173 |
2015 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
In contrast, NOTCH1 or K/N-RAS mutated CLL displayed normal responses in p53/ATM target gene induction and apoptosis.
|
25371178 |
2015 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Here, we showed that this assay is able to identify and distinguish three subgroups of CLL tumors (i.e., TP53-defective, ATM-defective and WT) and is also able to detect additional samples with a defective DDR, without molecular aberrations in TP53 and/or ATM.
|
26247737 |
2015 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
A robust response to ODN+IL-15 was positively linked to presence of chromosomal anomalies (trisomy-12 or ataxia telangiectasia mutated anomaly + del13q14) and negatively linked to a very high proportion of CD38(+) cells within the blood-derived B-CLL population.
|
26136429 |
2015 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia.
|
25840602 |
2015 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial.
|
24584352 |
2014 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL).
|
25010664 |
2014 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
The B-CLL fluorescence in situ hybridization (FISH) panel comprised ATM, CEP12, D13S25, and TP53 probes.
|
25301672 |
2014 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
In this review we discuss ATM function and the consequences of its loss during CLL pathogenesis, differences in clinical behavior of tumors with monoallelic and biallelic ATM alterations, and we outline possible approaches for targeting the ATM null CLL phenotype.
|
23906020 |
2014 |
Chronic Lymphocytic Leukemia
|
0.700 |
Biomarker
|
disease |
BEFREE |
Evidence suggests that tumor suppressor genes other than ATM are likely to be involved in CLL with del(11q).
|
24686393 |
2014 |
Chronic Lymphocytic Leukemia
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The in vitro treatment of primary B-CLL cells with the activator of p53 Nutlin-3 induced the transcription of p53 target genes, without significant differences between the B-CLL without mutations and those harboring either ATM or NOTCH1mutations.
|
25587027 |
2014 |