|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mutations in the RAS-BRAF-MAPK-ERK pathway define a specific subgroup of patients with adverse clinical features and provide new therapeutic options in chronic lymphocytic leukemia.
|
30262568 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Abbreviations: APC/C: Anaphase-Promoting Complex/Cyclosome; BAD: BCL2-Associated agonist of cell Death; BAK1: BCL2 Antagonist Kinase1; BAX: BCL2-Associated X; BCL2: B-cell Chronic Lymphocytic Leukaemia (CLL)/Lymphoma 2; BH: BCL2 Homology Domain; BID: BH3-Interacting domain Death agonist; BIM: BCL2-Interacting Mediator of cell death; BUB: Budding Uninhibited by Benzimidazoles; CDC: Cell Division Cycle; CDH1: Cadherin-1; CDK1: Cyclin-Dependent Kinase 1; CEP55: Centrosomal Protein (55 KDa): CIN: Chromosomal Instability; CTA: Cancer Testis Antigen; EGR1: Early Growth Response protein 1; ERK: Extracellular Signal-Regulated Kinase; ESCRT: Endosomal Sorting Complexes Required for Transport; GIN: Genomic Instability; MAD2: Mitotic Arrest Deficient 2; MCL1: Myeloid Cell Leukemia sequence 1; MPS1: Monopolar Spindle 1 Kinase; MYT1: MYelin Transcription factor 1; PLK1: Polo Like Kinase 1; PUMA: p53-Upregulated Mediator of Apoptosis; SAC: Spindle Assembly Checkpoint; TAA: Tumor-Associated Antigen.
|
30601084 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the human CLL NSG xenograft model, treatment with acalabrutinib demonstrated on-target effects, including decreased phosphorylation of PLCγ2, ERK, and significant inhibition of CLL cell proliferation.
|
27903679 |
2017 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
IgM signaling induced prolonged activation of ERK kinases and promoted CLL cell survival, CCL3 and CCL4 chemokine secretion, and downregulation of BCL6, the transcriptional repressor of CCL3 In contrast, IgD signaling induced activation of the cytoskeletal protein HS1, along with F-actin polymerization, which resulted in rapid receptor internalization and failure to support downstream responses, including CLL cell survival and chemokine secretion.
|
27534555 |
2016 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
BRAF inhibitor-driven ERK activity and CLL proliferation required B cell antigen receptor (BCR) activation, as inhibition of the BCR-proximal spleen tyrosine kinase (SYK) reversed ERK hyperactivation and proliferation of CLL cells from multiple patients, while inhibition of the BCR-distal Bruton tyrosine kinase had no effect.
|
25329694 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
We also found that blocking ET(A)R via BQ-123 interferes with ERK phosphorylation and CLL pro-survival effect mediated by B-cell receptor (BCR) activation.
|
24901342 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
After in vitro culture in the absence of stimulation, differences in p-ERK were identified at any time point, with higher p-ERK levels in U-CLL versus M-CLL.
|
24719462 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Cocultures with DHH-expressing BM stromal cells reduced sensitivity of CLLs to SMO-inhibitor treatment by activation of noncanonical ERK phosphorylation directly downstream of the PTCH1 receptor without involvement of SMO and could be overcome by the HH-blocking Ab 5E1 or a combination of SMO and ERK inhibitors.
|
22130798 |
2012 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Importantly, ex vivo CLL LN samples also displayed strong ERK activation together with high Bcl-xL and Mcl-1 but low Bim levels.
|
18796631 |
2008 |
|
Chronic Lymphocytic Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
To further define the relative contribution of the Akt and ERK kinases in regulating CLL B-cell survival, we introduced constitutively active mutants of Akt and MEK in primary CLL B cells and evaluated changes in the expression of relevant pro- and antiapoptotic proteins.
|
17928528 |
2008 |