Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
We showed that ectopic MCL1 expression rescued apoptosis of MM.
|
31653349 |
2020 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Preclinical evaluation of the simultaneous inhibition of MCL-1 and BCL-2 with the combination of S63845 and venetoclax in multiple myeloma.
|
31320555 |
2020 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
This work led to the discovery of <b>1</b>, a potent Mcl-1 inhibitor (IC<sub>50</sub> = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model.
|
31736296 |
2019 |
Multiple Myeloma
|
0.400 |
PosttranslationalModification
|
disease |
BEFREE |
Co-culture experiments resulted in MDSC-induced AMPK phosphorylation in MM cells, which was associated with an increase in the anti-apoptotic factors MCL-1 and BCL-2, and the autophagy-marker LC3II.
|
30419344 |
2019 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
In myeloma, in vitro sensitivity to venetoclax is mainly observed in plasma cells harboring the t(11;14) translocation, a molecular subgroup associated with high Bcl-2 and low Mcl-1/Bcl-XL expression.
|
30076373 |
2018 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Multiple myeloma is considered to be a disease dependent mainly on MCL1 for survival, based mostly on studies using cell lines.
|
30309889 |
2018 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
ABT-199 is a specific Bcl-2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co-expression of Mcl-1 and Bcl-xL.
|
29761903 |
2018 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Our studies demonstrate that AZD5991 binds directly to Mcl-1 and induces rapid apoptosis in cancer cells, most notably myeloma and acute myeloid leukemia, by activating the Bak-dependent mitochondrial apoptotic pathway.
|
30559424 |
2018 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Members of MCL1-M captured both MM cell-intrinsically acting signals and the signals regulating the interaction between MM cells with bone marrow microenvironment.
|
29696703 |
2018 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Expression of pro-survival BCL-2 family protein MCL-1 is essential for survival of malignant PC in multiple myeloma (MM).
|
30524962 |
2018 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
MCL-1 ectopic expression or knockdown in MM cells significantly diminished or increased ABT-199 sensitivity, respectively.
|
29241222 |
2018 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
In conclusion, the NEAT1/miR-193a/MCL1 pathway is closely associated with the development of DEX resistance in myeloma cells, and knockdown of NEAT1 can significantly improve DEX sensitivity in MM.
|
29205703 |
2018 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
We used the Bcl-2/Bcl-x<sub>L</sub> inhibitor ABT-737 to study the factors regulating whether myeloma is Mcl-1 dependent, and thus resistant to ABT-737-induced apoptosis, or Bcl-2/Bcl-x<sub>L</sub> codependent, and thus sensitive to ABT-737.
|
28151428 |
2017 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138<sup>+</sup> MM cells.
|
28938651 |
2017 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
The antiapoptotic proteins BCL-2 and myeloid cell leukemia sequence 1 (MCL-1) promote multiple myeloma (MM) cell survival.
|
28847998 |
2017 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-X<sub>L</sub> and MCL-1.
|
29018077 |
2017 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
We show that our lead compound (compound 20) decreases glucose uptake and cell proliferation as well as inhibits the expression of pro-survival MCL-1 in MM similar to the effect observed via knockdown of GLUT4 expression.
|
28837922 |
2017 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
IHC of multiple myeloma patient bone marrow biopsies and aspirates (n = 95) revealed high levels of BCL-2 and BCL-XL in 62% and 43% of evaluable samples, respectively, while 34% were characterized as BCL-2(High)/BCL-XL (Low) In addition to MCL-1, our data suggest that BCL-XL may also be a potential resistance factor to venetoclax monotherapy and in combination with bortezomib.
|
26939706 |
2016 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
These findings underscore the implication of the Mcl-1/Bak axis in myeloma cell death triggered by Thapsigargin.
|
27697610 |
2016 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
We also identified a previously unrecognized subset of myeloma that is highly BCLXL-dependent, and has the potential for cotargeting MCL1 and BCLXL.
|
27465916 |
2016 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
In conclusion, our data demonstrate that soluble factors from MM cells are able to generate MDSC through Mcl-1 upregulation and this cell population can be considered as a possible target in MM disease.
|
25871384 |
2015 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Usp24 was found to sustain myeloma cell survival and Mcl-1 regulation in the absence of Usp9x.
|
25814533 |
2015 |
Multiple Myeloma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.
|
25542900 |
2015 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Furthermore, previous studies demonstrated that proteasome inhibitors induce Mcl-1 accumulation that, in turn, slows down their pro-apoptotic effects, and the cell survival in multiple myeloma is highly dependent on Mcl-1.
|
25812695 |
2015 |
Multiple Myeloma
|
0.400 |
Biomarker
|
disease |
BEFREE |
miR-137 and miR-197 Induce Apoptosis and Suppress Tumorigenicity by Targeting MCL-1 in Multiple Myeloma.
|
25724519 |
2015 |