A5034550055- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- RNA modifications and cancer
- Chronic Myeloid Leukemia Treatments
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Cancer-related gene regulation
- HIV/AIDS drug development and treatment
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
- Cancer-related molecular mechanisms research
- HER2/EGFR in Cancer Research
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Bioactive Compounds and Antitumor Agents
- Immune cells in cancer
- Quinazolinone synthesis and applications
City Of Hope National Medical Center
2017-2025
City of Hope
2016-2025
Beckman Research Institute
2019-2025
Translational Genomics Research Institute
2023-2025
Research Medical Center
2022
Institute of Electrical and Electronics Engineers
2020
CeMM Research Center for Molecular Medicine
2019
Austrian Academy of Sciences
2019
University Medical Center HCMC
2018-2019
Stanford University
2013-2016
Abstract Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein N -methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid (AML), eliminates disease cancer-intrinsic mechanisms cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation AML decreased...
Significance Ribosomal proteins are synthesized in the nucleolus under control of a number repetitive DNA elements and required for cell proliferation. Cancer cells frequently contain mutations that activate phosphoinositide 3-kinase/Akt signaling pathway. This study shows activation Akt enhances transcription ribosomal genes by stabilizing protein, initiation factor I (TIF-IA), which is essential DNA. Activated also increases RNA synthesis phosphorylating casein kinase 2, turn...
Abstract Induction of reactive oxygen species (ROS), an important process for the cytotoxicity various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates NF‐E2‐related factor 2 (Nrf2) antioxidant response pathway which in turn results induction enzymes that neutralize ROS. In this study, we demonstrated Nrf2 inhibition is additional mechanism responsible marked antileukemic activity AML seen with combination HMAs and venetoclax (ABT‐199)....
BCL-2 inhibition through venetoclax (VEN) targets acute myeloid leukemia (AML) blast cells and leukemic stem (LSCs). Although VEN-containing regimens yield 60-70% clinical response rates, the vast majority of patients inevitably suffer disease relapse, likely because persistence drug-resistant LSCs. We previously reported preclinical activity ribonucleoside analog 8-chloro-adenosine (8-Cl-Ado) against AML Moreover, our ongoing phase I trial 8-Cl-Ado in with refractory/relapsed demonstrates...
Abstract Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant transcription and perturbed biogenesis via HDAC8/RAN-XPO5-RCC1 axis. Aberrant upregulation promotes survival leukemia-initiating progenitors is critical for initiating maintaining CM-driven AML. We enhances MYC activity SPRED1/PLK2-ERK-MYC Notably, genetic deletion significantly reduces AML rate...
Abstract The mechanisms underlying the transformation of chronic myeloid leukemia (CML) from phase (CP) to blast crisis (BC) are not fully elucidated. Here, we show lower levels miR-142 in CD34 + CD38 − blasts BC CML patients than those CP patients, suggesting that deficit is implicated evolution. Thus, create knockout (i.e., −/− BCR-ABL ) mice, which develop and die sooner wt +/+ instead remain CML. Leukemic stem cells (LSCs) mice recapitulate phenotype congenic recipients, supporting LSC...
The interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) bulk blasts and leukemic stem cells (LSCs), but not normal hematopoietic (HSCs), providing an opportunity to target eliminate the disease, while sparing hematopoiesis. Herein, we report activity of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE) in AML.
We reported that an acquired miR-142 deficit transforms chronic phase (CP) myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of in development and activity immune system, we postulated this also promotes LSC escape. Herein, report on IL-6-driven occurring T during BC transformation. In CML murine models, impairs thymic differentiation lymphoid-primed multipotent progenitors (LMPP) prevents cells' metabolic reprogramming, thereby leading to loss...
Ran is a small GTPase of the Ras superfamily that governs nucleocytoplasmic transport, including miR-126, microRNA supports homeostasis and expansion leukemia stem cells (LSCs). binds to Exportin 5 facilitate transport precursor (pre)-miR-126 across nuclear membrane for its maturation. Our goal inhibit prevent pre-miR-126 cytoplasm. Like other family proteins, targeting with molecules challenging due relatively flat surface lack binding cavities. Ran's activity regulated by long disordered...
<h3>Objective</h3> Human oesophageal stem cell research is hampered by the lack of an optimal assay system to study self-renewal and differentiation. We aimed identify characterise human mouse stem/progenitor cells establishing 3-dimensional organotypic sphere culture systems for both species. <h3>Design</h3> Primary epithelial were freshly isolated fluorescence-activated sorting (FACS)-sorted from oesophagus developed. The self-renewing potential differentiation status novel subpopulations...
The ErbB3-binding protein 1 (Ebp1) has been implicated in diverse cancers as having either oncogenic or tumor suppressor activities. present study was undertaken to determine the effects of Ebp1 expression AML cells and mechanisms by which promotes cell proliferation these cells.The studied mononuclear obtained from peripheral blood 54 patients with Western blot analysis. on proliferating nuclear antigen (PCNA) measured using analysis, immunoprecipitation, vitro ubiquitination,...
Venetoclax (VEN) in combination with hypomethylating agents induces disease remission patients de novo AML, however, most eventually relapse. AML relapse is attributed to the persistence of drug-resistant leukemia stem cells (LSCs). LSCs need maintain low intracellular levels reactive oxygen species (ROS). Arsenic trioxide (ATO) apoptosis via upregulation ROS-induced stress DNA-repair mechanisms. Elevated ROS can trigger Nrf2 antioxidant pathway counteract effects high levels. We...
Significance We report on a deregulatory activity microRNA (miRNA) biogenesis by the FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) in acute myeloid leukemia. FLT3-ITD provides divergent signal for concurrent and aberrant miR-155 up-regulation miR-126 down-regulation via series of miRNA–protein regulatory loops interconnected through SH2-containing inositol phosphatase 1 (SHIP1)/phosphor-protein B (AKT)/Sprouty related EVH1 domain containing (SPRED1) signaling. This...
Although the overall survival rate of B cell acute lymphoblastic leukemia (B-ALL) in childhood is more than 80%, it merely 30% refractory/relapsed and adult patients with B-ALL. This demonstrates a need for improved therapy targeting this subgroup Here, we show that ten-eleven translocation 1 (TET1) protein, dioxygenase involved DNA demethylation, overexpressed plays crucial oncogenic role independent its catalytic activity Consistent B-ALL, overexpression TET1 alone normal precursor cells...