A5031885180- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Chronic Myeloid Leukemia Treatments
- Retinoids in leukemia and cellular processes
- Acute Lymphoblastic Leukemia research
- Phagocytosis and Immune Regulation
- Protein Kinase Regulation and GTPase Signaling
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Chronic Lymphocytic Leukemia Research
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Cytokine Signaling Pathways and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- Advanced biosensing and bioanalysis techniques
- Autophagy in Disease and Therapy
University of Colorado Denver
2018-2024
University of Colorado Anschutz Medical Campus
2018-2024
University of California, San Francisco
2016-2021
Pediatrics and Genetics
2020
Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well relapse following initial response demonstrates the need for a deeper understanding mechanisms. In present study, we report that to venetoclax +azacitidine AML correlate closely developmental stage, where phenotypically primitive is sensitive, but monocytic more resistant. Mechanistically, resistant has distinct...
Venetoclax (ven) plus azacitidine (aza) is the standard of care for patients with newly diagnosed acute myeloid leukemia (AML) who are not candidates intensive chemotherapy (IC). Some IC instead receive ven/aza. We retrospectively analyzed AML received ven/aza (n = 143) or 149) to compare outcomes, seek variables that could predict response 1 therapy other, and ascertain whether treatment recommendations be refined. The rates were 76.9% 70.5% IC. median overall survival (OS) was 884 days...
Abstract The BCL2 inhibitor venetoclax has recently emerged as an important component of acute myeloid leukemia (AML) therapy. Notably, use this agent revealed a previously unrecognized form pathogenesis characterized by monocytic disease progression. We demonstrate that arises from fundamentally different type stem cell (LSC), which we designate LSC (m-LSC), is developmentally and clinically distinct the more well-described primitive (p-LSC). m-LSC distinguished unique immunophenotype...
Acute myeloid leukemia stem cells (LSCs) are uniquely reliant on oxidative phosphorylation (OXPHOS) for survival. Moreover, maintenance of OXPHOS is dependent BCL-2, creating a therapeutic opportunity to target LSCs using the BCL-2 inhibitor venetoclax. Although venetoclax-based regimens have shown promising clinical activity, emergence drug resistance prevalent. Thus, in present study, we investigated how mitochondrial properties may influence venetoclax responsiveness. Our data show that...
Abstract Due to the disseminated nature of leukemia, malignant cells are exposed many different tissue microenvironments, including a variety extramedullary sites. In present study, we demonstrate that leukemic residing in liver display unique biological properties and also contribute systemic changes influence physiologic responses chemotherapy. Specifically, microenvironment induces metabolic adaptations via upregulating expression endothelial lipase leukemia cells, which not only...
Abstract Oncogenic KRAS mutations introduce discrete amino acid substitutions that reduce intrinsic Ras GTPase activity and confer resistance to GTPase-activating proteins (GAPs). Here we discover a partial duplication of the switch 2 domain K-Ras encoding tandem repeat acids G60_A66dup in child with an atypical myeloproliferative neoplasm. containing this or similar five E62_A66dup mutation identified lung colon cancers transform growth primary myeloid progenitors Ba/F3 cells. Recombinant...
We previously reported that acute myeloid leukemia stem cells (LSCs) are uniquely reliant on oxidative phosphorylation (OXPHOS) for survival. Moreover, maintenance of OXPHOS is dependent BCL2, creating a therapeutic opportunity to target LSCs using the BCL2 inhibitor drug venetoclax. While venetoclax-based regimens have indeed shown promising clinical activity, emergence resistance prevalent. Thus, in present study, we investigated how mitochondrial properties may influence mechanisms...
Signal transducer and activator of transcription 3 (STAT3) is a well-described factor that mediates oxidative phosphorylation glutamine uptake in bulk acute myeloid leukemia (AML) cells leukemic stem (LSCs). STAT3 has also been shown to translocate the mitochondria AML cells, particularly when phosphorylated at serine 727 (pSTAT3 S727) residue. Inhibition results impaired mitochondrial function decreased cell viability. We discovered novel interaction with voltage-dependent anion channel 1...
Abstract The BCL-2 inhibitor venetoclax has recently emerged as an important component of acute myeloid leukemia (AML) therapy. Notably, use this agent revealed a previously unrecognized form pathogenesis characterized by monocytic disease progression. We demonstrate that arises from fundamentally different type stem cell (LSC), which we designate LSC (m-LSC), is developmentally and clinically distinct the more well-described primitive (p-LSC). m-LSC distinguished unique immunophenotype...
<p>Supplementary Fig. 1: Immunophenotyping and WES analysis of primary AML specimens. Supplementary 2: engrafted cells in PDX. 3: remission duration VEN/AZA relapsed patients. 4: CITE-seq data analysis. 5: Sorting strategies for determining m-LSC immunophenotype expression various LSC markers m-LSCs. 6: Molecular properties targeting m-LSCs vitro vivo. 7: M5 but not M4 patients showing significantly higher refractory rate to therapy.</p>
<p>Supplementary Fig. 1: Immunophenotyping and WES analysis of primary AML specimens. Supplementary 2: engrafted cells in PDX. 3: remission duration VEN/AZA relapsed patients. 4: CITE-seq data analysis. 5: Sorting strategies for determining m-LSC immunophenotype expression various LSC markers m-LSCs. 6: Molecular properties targeting m-LSCs vitro vivo. 7: M5 but not M4 patients showing significantly higher refractory rate to therapy.</p>