A5015097694- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Multiple Myeloma Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Retinoids in leukemia and cellular processes
- Chronic Lymphocytic Leukemia Research
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- Childhood Cancer Survivors' Quality of Life
- Cancer, Hypoxia, and Metabolism
- Medication Adherence and Compliance
- Neutropenia and Cancer Infections
- Hemoglobinopathies and Related Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Iron Metabolism and Disorders
Children's Healthcare of Atlanta
2023-2025
Emory University
2023-2025
University of Colorado Denver
2017-2024
Center for Cancer and Blood Disorders
2018-2024
University of Colorado Anschutz Medical Campus
2017-2024
Children's Hospital Colorado
2017-2024
Children's Center
2023
Cystic Fibrosis Foundation
2023
Cedars-Sinai Medical Center
2023
Health Outcomes Solutions (United States)
2022
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...
Key Points Responses and survival with venetoclax for “real-world” AML patients were promising but inferior to those treated in a clinical trial. Compared induction, response rates are as high would be predicted had lower than expected early death rate.
Abstract Myelodysplastic syndrome (MDS) is a chronic hematologic disorder that frequently evolves to more aggressive stages and in some cases leads acute myeloid leukemia (AML). MDS arises from mutations hematopoietic stem cells (HSCs). Thus, define optimal therapies, it essential understand molecular events driving HSC pathogenesis. In this study, we report during evolution of MDS, malignant HSCs activate distinct cellular programs render such susceptible therapeutic intervention....
Abstract Background The BCL‐2 inhibitor venetoclax (ven) has revolutionized the treatment of acute myeloid leukemia (AML) in elderly adults, leading to its recent FDA approval for this population combination regimens. Although extensive data exist adult malignancies, there are limited preclinical on efficacy and/or dosing pediatric myelodysplastic syndrome (MDS) or AML and thus little information guide use regimen patients. Our objective was describe our single‐center experience with...
Allogeneic hematopoietic stem cell transplantation (SCT) after a patient with acute myeloid leukemia (AML) achieves remission from intensive chemotherapy (IC) is given curative intent. Recently, venetoclax-based regimens have become the standard of care for patients newly diagnosed AML who are unfit IC. If these achieve remission, they may also be considered potentially consolidation SCT. There limited data comparing outcomes SCT different induction strategies. The purpose current study was...
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...
Myelodysplastic syndrome (MDS) is a group of heterogeneous disorders caused by ineffective hematopoiesis and characterized bone marrow dysplasia cytopenia. Current treatment options for MDS are limited to supportive care, hypomethylating agents, stem cell transplant. Most patients eventually succumb the disease or progress leukemia. Previously, we found that CD123 can be used delineate cells in at high risk CD123-positive population biologically distinct from normal hematopoietic cells....
Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) whom intensive chemotherapy inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial investigate two hypotheses: i) higher doses venetoclax tolerable and more effective, ii) azacitidine can be discontinued after deep remissions. Forty-two newly diagnosed AML were enrolled in investigator-initiated High Dose Discontinuation Azacitidine+Venetoclax...
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...