Mitophagy promotes resistance to BH3 mimetics in acute myeloid leukemia
BH3 mimetics are used as an efficient strategy to induce cell death in several blood
malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 …
malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 …
[HTML][HTML] Reduced mitochondrial apoptotic priming drives resistance to BH3 mimetics in acute myeloid leukemia
Acquired resistance to BH3 mimetic antagonists of BCL-2 and MCL-1 is an important clinical
problem. Using acute myelogenous leukemia (AML) patient-derived xenograft (PDX) models …
problem. Using acute myelogenous leukemia (AML) patient-derived xenograft (PDX) models …
Maximal Activation of Apoptosis Signaling by Cotargeting Antiapoptotic Proteins in BH3 Mimetic–Resistant AML and AML Stem Cells
BZ Carter, PY Mak, W Tao, Q Zhang, V Ruvolo… - Molecular cancer …, 2022 - AACR
MCL-1 is known to play a major role in resistance to BCL-2 inhibition, but the contribution of
other BCL-2 family proteins has not been fully explored. We, here, demonstrate the …
other BCL-2 family proteins has not been fully explored. We, here, demonstrate the …
[HTML][HTML] Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia
Several chemo-resistance mechanisms including the Bcl-2 protein family overexpression
and constitutive activation of the PI3K/Akt/mTOR signaling have been documented in acute …
and constitutive activation of the PI3K/Akt/mTOR signaling have been documented in acute …
BH3 mimetics in AML therapy: death and beyond?
B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics are targeted therapeutic
agents that allow response prediction and patient stratification. BH3 mimetics are …
agents that allow response prediction and patient stratification. BH3 mimetics are …
Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia
DM Moujalled, G Pomilio, C Ghiurau, A Ivey, J Salmon… - Leukemia, 2019 - nature.com
Improving outcomes in acute myeloid leukemia (AML) remains a major clinical challenge.
Overexpression of pro-survival BCL-2 family members rendering transformed cells resistant …
Overexpression of pro-survival BCL-2 family members rendering transformed cells resistant …
[HTML][HTML] AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia
AMP-activated protein kinase (AMPK) regulates the balance between cellular anabolism
and catabolism dependent on energy resources to maintain proliferation and survival. Small …
and catabolism dependent on energy resources to maintain proliferation and survival. Small …
[HTML][HTML] Concomitantly targeting BCL-2 with venetoclax (ABT-199/GDC-0199) and MAPK signaling with Cobimetinib (GDC-0973) in acute myeloid leukemia models
Pro-survival molecules including BCL-2 play critical roles in leukemia transformation and
chemoresistance. ABT-199/GDC-0199 (venetoclax) is an orally available BH3-mimetic that …
chemoresistance. ABT-199/GDC-0199 (venetoclax) is an orally available BH3-mimetic that …
Multiple BH3 mimetics antagonize antiapoptotic MCL1 protein by inducing the endoplasmic reticulum stress response and up-regulating BH3-only protein NOXA
TC Albershardt, BL Salerni, RS Soderquist… - Journal of Biological …, 2011 - ASBMB
BH3 mimetics are small molecules designed or discovered to mimic the binding of BH3-only
proteins to the hydrophobic groove of antiapoptotic BCL2 proteins. The selectivity of these …
proteins to the hydrophobic groove of antiapoptotic BCL2 proteins. The selectivity of these …
Systematic mapping of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity
RS Soderquist, L Crawford, E Liu, M Lu… - Nature …, 2018 - nature.com
While inhibitors of BCL-2 family proteins (BH3 mimetics) have shown promise as anti-cancer
agents, the various dependencies or co-dependencies of diverse cancers on BCL-2 genes …
agents, the various dependencies or co-dependencies of diverse cancers on BCL-2 genes …