A5045966693- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Neutropenia and Cancer Infections
- Immune cells in cancer
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Renal Transplantation Outcomes and Treatments
- Multiple Myeloma Research and Treatments
- Childhood Cancer Survivors' Quality of Life
- Cancer survivorship and care
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Bone health and treatments
- Primary Care and Health Outcomes
- MicroRNA in disease regulation
- Diversity and Career in Medicine
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Oregon Health & Science University
2019-2025
The Ohio State University
2012-2018
Comprehensive Blood & Cancer Center
2018
Michigan State University
2010
Day Family Medicine
1991-2010
Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity genomic, transcriptomic, and clinical annotations for large cohort AML patients, which facilitated discovery functional genomic correlates. Here, we present dataset that has been harmonized our initial report to yield cumulative 805 patients (942 specimens). show strong cross-cohort concordance identify features response. Further, deconvoluting...
Significance Acute myeloid leukemia (AML) is the most common acute in adults, with a 5-y survival of 29%. Immunotherapy based on premise that tumors suppress immune system. We investigated status T cell immunity AML at time diagnosis. found significant association between percentage bone marrow and overall newly diagnosed patients. When we evaluated cells from patients AML, one-third displayed profound functional impairment. Most these compromised cells, however, could be rescued using...
Risk stratification in acute myeloid leukemia (AML) remains principle survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN) recommendations were recently published, with notable updates to risk group assignment. complexity of comparative outcomes between the 2017 ELN guidelines unknown. This analysis evaluated criteria patients enrolled within multicenter Beat AML cohort. Five hundred thirteen included. Most had 1 or 2 risk-defining abnormalities. In ≥2...
SMAD4 is the only common SMAD in TGF-β signaling that usually impedes immune cell activation tumor microenvironment. However, we demonstrated here selective deletion of Smad4 NK cells actually led to dramatically reduced rejection and augmented metastases, murine CMV clearance, as well impeded homeostasis maturation. This was associated with a downregulation granzyme B (Gzmb), Kit, Prdm1 Smad4-deficient cells. We further unveiled mechanism by which promotes Gzmb expression. identified direct...
Abstract The BCL2 inhibitor venetoclax combined with the hypomethylating agent azacytidine shows significant clinical benefit in a subset of patients acute myeloid leukemia (AML); however, resistance limits response and durability. We prospectively profiled ex vivo activity 25 venetoclax-inclusive combinations on primary AML patient samples to identify those improved potency synergy compared + (Ven azacytidine). Combination sensitivities correlated tumor cell state discern three patterns:...
Despite prophylaxis, acute graft-versus-host disease (aGVHD) occurs in up to 40% 60% of patients undergoing an allogeneic hematopoietic stem cell transplantation (alloHSCT). Tacrolimus remains a common GVHD prophylactic medication used combination with mycophenolate or methotrexate. The purpose this study was compare tacrolimus levels day +56 clinical outcomes who underwent alloHSCT. This retrospective cohort adult alloHSCT between January 2009 and April 2019 at Oregon Health Science...
ABSTRACT Cytomegalovirus (CMV) infection post‐hematopoietic cell transplantation (HCT) remains a significant cause of morbidity and mortality. While letermovir prophylaxis is available for CMV‐seropositive recipients, optimal donor selection CMV‐seronegative recipients unclear, with age often prioritized over CMV serostatus. We investigated the relative impact serostatus in ( n = 1013) either 318) or donors 695), who underwent HCT HLA‐matched sibling calcineurin inhibitor‐based...
Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns about non-relapse mortality (NRM) in limit allo-HCT utilization. We executed a prospective, observational study (BMT-CTN 1704) enrolling recipients aged ≥60 years from 49 centers the U.S. analyzed associations between 13 measurements of adult health and NRM within 1-year to construct comprehensive assessment risk model (primary-CHARM) using amultivariate...
Abstract Background: NCAM1 (CD56) is a neural cell adhesion molecule that expressed on immune cells including NK cells, T dendric and monocytes. Acute myeloid leukemia (AML) patients also aberrantly express in around 30% of cases which may impact treatment response. Our group recently found CD56 expression blasts associated with worse overall survival to the BCL2 inhibitor, Venetoclax (VEN), VEN combined hypomethylating agents or JAK Ruxolitinib. Within molecular prognostic risk score (mPRS)...
Abstract Resistance to venetoclax-based therapy in acute myeloid leukemia (AML) includes genetic (i.e., mutations N/KRAS, FLT3-ITD, TP53) and phenotypic monocytic differentiation) features. Whether differentiation contributes clinical venetoclax resistance secondary a bias remains unknown. This multimodal, multicenter, international analysis inclusive of 678 patients comprehensively characterized the prognostic role AML treated with hypomethylating agents combined venetoclax. genetics (HR:...