A5010440853- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Histone Deacetylase Inhibitors Research
- Lung Cancer Treatments and Mutations
- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Multiple Myeloma Research and Treatments
- Extracellular vesicles in disease
- Biochemical and Molecular Research
- Blood transfusion and management
- Osteoarthritis Treatment and Mechanisms
- DNA Repair Mechanisms
- Acute Lymphoblastic Leukemia research
- Metal complexes synthesis and properties
- Retinoids in leukemia and cellular processes
- Bone and Joint Diseases
- Acute Ischemic Stroke Management
Wayne State University
2020-2025
The Barbara Ann Karmanos Cancer Institute
2020-2025
Jinzhou Medical University
2019-2025
Jilin University
2016-2024
West China Hospital of Sichuan University
2019
Sichuan University
2019
Abstract Eradication of acute myeloid leukemia (AML) is therapeutically challenging; many patients succumb to AML despite initially responding conventional treatments. Here, we showed that the imipridone ONC213 elicits potent antileukemia activity in a subset cell lines and primary patient samples, particularly stem cells, while producing negligible toxicity normal hematopoietic cells. suppressed mitochondrial respiration elevated α-ketoglutarate by suppressing dehydrogenase (αKGDH)...
Induction therapy for patients with acute myeloid leukemia (AML) has remained largely unchanged over 40 years, while overall survival rates remain unacceptably low, highlighting the need new therapies. The PI3K/Akt pathway is constitutively active in majority of AML. Given that histone deacetylase inhibitors have been shown to synergize PI3K preclinical AML models, we investigated novel dual-acting and inhibitor CUDC-907 cells both vitro vivo. We demonstrated induces apoptosis cell lines...
Abstract Venetoclax, an FDA-approved Bcl-2 selective inhibitor for the treatment of chronic lymphocytic leukemia and acute myeloid (AML), is tolerated well in elderly patients with AML has good overall response rates; however, resistance remains a concern. In this study, we show that targeting CDK9 voruciclib combination venetoclax results synergistic antileukemic activity against cell lines primary patient samples. inhibition enhances through downregulation Mcl-1 c-Myc. However, transient,...
Abstract Acute myeloid leukemia (AML) continues to be a challenging disease treat, thus new treatment strategies are needed. In this study, we investigated the antileukemic effects of ATR inhibition alone or combined with cytarabine in AML cells. Treatment ATR-selective inhibitor AZ20 caused proliferation cell lines and primary patient samples. It partially abolished G2 cycle checkpoint DNA replication stress damage, accompanied by CDK1-independent apoptosis downregulation RRM1 RRM2....
Abstract The antiapoptotic Bcl‐2 family proteins play critical roles in resistance to chemotherapy acute myeloid leukaemia ( AML ). Bcl‐2‐selective inhibitor ABT ‐199 (Venetoclax) shows promising antileukaemic activity against , though Mcl‐1 limits its activity. XPO 1 is a nuclear exporter overexpressed cells and inhibition decreases levels cancer cells. Thus, we hypothesized that the 1‐selective KPT ‐330 (Selinexor) can synergize with induce apoptosis through down‐regulation of Mcl‐1....
Venetoclax is a promising agent in the treatment of acute myeloid leukemia, though its antileukemic activity limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways enhance venetoclax activity. In this study, we combine with dual PI3K histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, induce damage, well c-Myc. We establish that CUDC-907 synergistically apoptosis leukemia cell lines...
Abstract Background Venetoclax + azacitidine is a frontline treatment for older adult acute myeloid leukemia (AML) patients and salvage therapy relapsed/refractory who have been treated with intensive chemotherapy. While this an important option, many fail to achieve complete remission of those that do, majority relapse. Leukemia stem cells (LSCs) are believed be responsible AML relapse can targeted through oxidative phosphorylation reduction. We previously reported ONC213 disrupts decreases...
Targeting oxidative phosphorylation (OXPHOS) is a promising strategy to improve treatment outcomes of acute myeloid leukemia (AML) patients. IACS-010759 mitochondrial complex I inhibitor that has demonstrated preclinical antileukemic activity and being tested in Phase clinical trials. However, deficiency been reported inhibit apoptotic cell death through prevention cytochrome c release. Thus, combining with BH3 mimetic may overcome this mechanism resistance leading synergistic against AML....
Abstract About 25% of patients with acute myeloid leukemia (AML) harbor FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations and their prognosis remains poor. Gilteritinib is a FLT3 inhibitor approved by the US FDA for use in adult FLT3-mutated relapsed or refractory AML patients. Monotherapy, while efficacious, shows short-lived responses, highlighting need combination therapies. Here we show that gilteritinib CUDC-907, dual PI3K histone deacetylases,...
Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) patients who are over the age of 75 cannot tolerate standard chemotherapy. Despite high response rates these therapies, most succumb disease due relapse and/or drug resistance, providing an unmet clinical need for novel therapies improve AML patient survival. ME-344 potent isoflavone demonstrated inhibitory activity toward oxidative...
<b>Abstract ID 95704</b> <b>Poster Board 261</b> Acute myeloid leukemia (AML) overall survival rates remain unacceptably low. Hence, new drugs are needed to improve survival. The imipridone family of anticancer agents have shown efficacy against various cancers, including AML. Thus, we investigated the and mechanism action novel imipridone, ONC213, in preclinical AML models. cell lines primary patient samples showed varying degrees sensitivity ONC213. However, ONC213 uniformly suppressed...
<p>THP-1 metabolomics data</p>
<p>Supplementary Figure S5</p>