|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
No statistically significant differences were found between the studied genes and prognosis stratifications, but Bcl-xl, Bak, cIAP1, and Mcl-1, LC3 were expressed at lower levels in the unfavorable AML group compared to the controls.
|
31434075 |
2020 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Mechanistically, we showed that SACLAC treatment led to reduced levels of splicing factor SF3B1 and alternative Mcl-1 mRNA splicing in multiple human AML cell lines.
|
31744877 |
2020 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
By comparing the expression levels of one probe with known sequences from each of the three genes, we identified several key genes, induced myeloid leukemia cell differentiation protein (Mcl1), far upstream element-binding protein 1 (Fubp1), and tumor protein D52-like 2 (Tpd52l2), which play important roles in acute lymphocytic leukemia and acute myelocytic leukemia.
|
31467227 |
2020 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The anti-apoptotic factors Mcl-1, Bcl-2, and Bcl-xL were also found to be over-expressed in acute myeloid leukemia (AML) (Kaufmann et al., 2016) and acute lymphocytic leukemia (ALL) (Findley, Gu, Yeager, & Zhou, 1997), suggesting that dis-regulated apoptotic processes could be a factor in the instigation of leukemia and/or its relapse.
|
30347215 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
We have recently revealed that FLT3-ITD confers resistance to the PI3K/AKT pathway inhibitors by protecting the mTORC1/4EBP1/Mcl-1 pathway through Pim kinases induced by STAT5 activation in AML.
|
30472492 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
We performed a side-by-side comparison of different highly selective and potent BH3-mimetics targeting BCL-2 (ABT-199), MCL-1 (S63845) or BCL-x<sub>L</sub> (A1331852) in a panel of AML cell lines and primary patient cells.
|
31801941 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, multiple AML mouse models and AML cell lines were sensitive to the MCL-1-selective antagonist A-1210477.
|
31612056 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia.
|
30214012 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here, we review the role of MCL-1 in AML and the mechanisms by which the potent cyclin-dependent kinase 9 inhibitor alvocidib, through regulation of MCL-1, may serve as a rational therapeutic approach against the disease.
|
30815228 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia.
|
31718075 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Together, our findings suggest that Mcl-1 and Akt phosphorylation are potential therapeutic targets for p53 mutants and that cabozantinib is an effective treatment in cytarabine-resistant FLT3-ITD-positive AML.
|
30862120 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
FLT3 inhibitors downregulate MCL1 and synergize with venetoclax in preclinical AML models.<i>See related article by Ma et al., p. 6815</i>.
|
31515455 |
2019 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Venetoclax (ABT-199) targets BCL-2 and has shown promising efficacy in AML but over-expression of MCL-1 can cause resistance.
|
30701031 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Cyclin-dependent kinase 9 (CDK9), a transcriptional activator necessary for the expression of MCL-1, represents a promising target for future AML therapies.
|
30132679 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Decrease in Mcl-1 protein expression was abrogated by treatment with the proteasome inhibitor MG132, and was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel mechanism of Mcl-1 regulation in AML.<b>Conclusions:</b> The data support clinical testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML.<i></i>.
|
29074603 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, Mcl-1 and Survivin can be considered as promising molecular targets for the treatment of AML.
|
29113504 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Inhibition of XPO1 enhances cell death induced by ABT-199 in acute myeloid leukaemia via Mcl-1.
|
30596398 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Armed with novel MCL1 inhibitors and the potent BCL2 inhibitor venetoclax, it may be possible to selectively induce apoptosis by combining or thoughtfully sequencing these inhibitors based on a rational evaluation of AML.<i>See related commentary by Leber et al., p. 1511</i>.<i>This article is highlighted in the In This Issue feature, p. 1494</i>.
|
30185627 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using inducible vectors and venetoclax to differentially target anti-apoptotic BCL-2 family members, BCL-2 and MCL1 emerged as critical and complementary proteins regulating cell survival in acute myeloid leukemia.
|
28751770 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results indicate that Bcl-2/Bcl-X<sub>L</sub> and Mcl-1 act in a redundant fashion as effectors of BMM-mediated AML drug resistance and highlight the potential of Mcl-1-repression to revert BMM-mediated drug resistance in the leukemic stem cell population, thus, prevent disease relapse and ultimately improve patient survival.
|
30361682 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia.
|
30559424 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Venetoclax/GDC-0980 coadministration induced rapid and pronounced BAX mitochondrial translocation, cytochrome c release, and apoptosis in various AML cell lines in association with AKT/mTOR inactivation and MCL-1 downregulation; ectopic expression of MCL-1 significantly protected cells from this regimen.
|
29559471 |
2018 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using dynamic BH3 profiling, we show that the agent TG02, which downregulates MCL-1, sensitises to the BCL-2-inhibitory BAD-BH3 peptide, whereas the BCL-2 antagonist ABT-199 sensitises to MCL-1 inhibitory NOXA-BH3 peptide in acute myeloid leukaemia (AML) cells.
|
27092880 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
Targeting sphingosine kinase 1 induces MCL1-dependent cell death in acute myeloid leukemia.
|
27956387 |
2017 |
|
Leukemia, Myelocytic, Acute
|
0.100 |
Biomarker
|
disease |
BEFREE |
The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells.
|
28211885 |
2017 |