A5007311119- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Chemokine receptors and signaling
- Protein Degradation and Inhibitors
- X-ray Diffraction in Crystallography
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Crystallization and Solubility Studies
- T-cell and B-cell Immunology
- Sesquiterpenes and Asteraceae Studies
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- Protease and Inhibitor Mechanisms
- Magnolia and Illicium research
- Bioactive Natural Diterpenoids Research
- Biosimilars and Bioanalytical Methods
- Glycosylation and Glycoproteins Research
- Histone Deacetylase Inhibitors Research
- Logic, programming, and type systems
- Iron Metabolism and Disorders
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Logic, Reasoning, and Knowledge
- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
University of Arkansas for Medical Sciences
2020-2025
Winthrop Rockefeller Foundation
2022-2024
Cornell University
1991-2019
University of Passau
1991
Linköping University
1991
Abstract Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T of are rare. One potential reason is that small subset minimal residual cells seeds relapse. Residual BCMA-CAR-T-mediated show less-differentiated features and express stem-like genes, including CD24. CD24-positive large fraction after BCMA-CAR-T therapy....
Abstract Current standard predictive models of disease risk do not adequately account for the heterogeneity survival outcomes in patients with new‐diagnosed multiple myeloma (NDMM). In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM identified prognostic impact all features. Using top‐ranked features, a weighted Myeloma Prognostic Score System (MPSS) model was formulated validated to predict overall (OS). training cohort, elevated lactate...
Multiple myeloma (MM) growth is supported by an immune-tolerant bone marrow microenvironment. Here, we find that loss of Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) tumor microenvironmental cells associated with MM suppression. The absence NEK2 leads to both fewer tumor-associated macrophages (TAMs) and inhibitory T cells. expression myeloid progenitor promotes the generation functional TAMs when stimulated conditional medium. Clinically, high increased CD8+ effector memory cells,...
Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138+ cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor (scBCR-seq), we differentiate monoclonal/neoplastic polyclonal/normal PCs find more dysregulated genes, especially in precursor patients, than would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes contribute to disease pathobiology,...
Autologous stem cell transplantation (ASCT) has been a mainstay in myeloma treatment for over three decades, but patient prognosis post-ASCT varies significantly. In retrospective study of 5259 patients with multiple (MM) at the University Arkansas Medical Sciences undergoing ASCT median 57-month follow-up, we divided dataset into training (70%) and validation (30%) subsets. Employing univariable multivariable Cox analyses, systematically assessed 29 clinical variables, identifying crucial...
Abstract Tumor immune microenvironmental alterations occur early in multiple myeloma (MM) development. In this study, we aim to systematically characterize the tumor microenvironment (TME) and tumor-immune interactions from precursor stages, i.e., monoclonal gammopathy of undetermined significance (MGUS) smoldering MM (SMM), newly diagnosed MM, comparing these healthy donors. Using CIBERSORT, mass cytometry (CyTOF), single-cell RNA sequencing (scRNA-Seq), examined innate adaptive changes...
The Second Revision of the International Staging System (R2-ISS) was published in 2022 and has been validated several cohorts patients with multiple myeloma (MM). In this study, we investigated a total 860 MM who received an upfront autologous stem cell transplantation between 2001 2021. median age 60 years, overall survival (OS) 123 months progression-free (PFS) 70 months. We collected variables included ISS, R-ISS, R2-ISS systems as well additional standard variables. Our analyses...
Key Points A-PACs target primary AML cells, sparing healthy CD34+ cord blood cells in vitro and reducing tumor burden with vivo treatment. NF-κB activation plays a role A-PAC–induced cell death.
Dehydroleucodine is a bioactive sesquiterpene lactone. Herein, four dehydroleucodine amino derivatives were synthesized using the amines proline, piperidine, morpholine, and tyramine, spectroscopic methods single-crystal X-ray diffraction unambiguously established their structures. The cytotoxic activity of these compounds was evaluated against eight acute myeloid leukemia cell lines, toxicity to peripheral blood mononuclear cells also determined. proline adduct most active compound, it...
A method to identify anticancer compounds in plants was proposed based on the hypothesis that these are primarily present provide them with an ecological advantage over neighboring and other competitors. According this view, identifying contain inhibit or interfere development of plant species may facilitate discovery novel agents. The developed tested using Magnolia grandiflora, Gynoxys verrucosa, Picradeniopsis oppositifolia, Hedyosmum racemosum, which known possess cytotoxic activities....
Background: Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Elevated serum markers are currently used to stratify MGUS patients into clinical risk groups. A molecular signature predicting progression has not been produced.Methods: Oligonucleotide microarray analysis mRNA isolated from CD138-selected bone marrow plasma cells 334 with stable disease and 40 that progressed MM within 10 years, was define a risk.Findings: After 3-fold...
We have previously demonstrated that cystatin E/M (CST6), which is elevated in a subset of patients with multiple myeloma (MM) lacking osteolytic lesions (OLs), suppresses MM bone disease by blocking osteoclast differentiation and function. CST6 secreted type 2 cystatin, cysteine protease inhibitor regulates lysosomal proteases the asparaginyl endopeptidase legumain. Here, we developed B cell maturation antigen (BCMA) chimeric receptor T cells (CAR-T cells), lysed released proteins. Our...