A5069157698- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Chromatin Remodeling and Cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- RNA regulation and disease
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Synthesis and Biological Evaluation
- RNA Research and Splicing
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Phytochemical compounds biological activities
- Electron and X-Ray Spectroscopy Techniques
- Advanced Electron Microscopy Techniques and Applications
- Advanced X-ray Imaging Techniques
- Erythrocyte Function and Pathophysiology
Icahn School of Medicine at Mount Sinai
2016-2024
Cancer Genetics (United States)
2018
New York Structural Biology Center
2016
Integrative multiomics analysis of myeloma identifies 12 disease subtypes defined by specific patterns genetic alterations.
B-cell maturation antigen (BCMA)-directed chimeric receptor T-cell (CAR T) therapy has demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma, and now there are two US Food Drug Administration-approved BCMA-directed CAR T products. However, despite high initial response rates, most eventually relapse. The outcomes of disease recurrence after have not been comprehensively studied, such an analysis would help define optimal treatment strategies. We analyzed the...
First-degree relatives of patients with multiple myeloma are at increased risk for the disease, but contribution pathogenic germline variants (PGV) in hereditary cancer genes to and outcomes is not well characterized. To address this, we analyzed exomes two independent cohorts 895 786 myeloma. PGVs were identified 8.6% Discovery cohort 11.5% Replication cohort, a notable presence high- or moderate-penetrance (associated autosomal dominant predisposition) DNA repair (3.6% 4.1%, respectively)....
Abstract Purpose: Somatic mutations in cancer cells can give rise to novel protein sequences that be presented by antigen-presenting as neoantigens the host immune system. Tumor represent excellent targets for immunotherapy, due their specific expression tissue. Despite widespread use of immunomodulatory drugs and immunotherapies recharge T NK cells, there has been no direct evidence neoantigen-specific T-cell responses are elicited multiple myeloma. Experimental Design: Using...
T-cell redirection therapy using chimeric antigen receptor (CAR) T cells and bispecific antibodies (BiAbs) has shown promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), leading to the approval of 2 CAR products numerous BiAb trials. Data on outcomes after relapse following BiAbs are urgently required develop strategies for sequencing salvage therapies. We identified 58 progressing a trial at Mount Sinai Hospital. Progression-free survival (PFS)...
While therapies targeting CD19 by antibodies, CAR-T cells and T cell engagers have improved the response rates in B-cell malignancies; emergence of resistant populations with low expression can lead to relapsed disease. We developed an vitro model adaptive resistance facilitated chronic exposure leukemia a CD19-immunotoxin. Single-cell (sc) RNAseq showed increase transcriptionally distinct CD19low cells. Mass cytometry demonstrated that CD22 was also decreased these ATAC-seq chromatin...
Purpose Multiple myeloma (MM) is a malignancy of plasma cells, with median survival 6 years. Despite recent therapeutic advancements, relapse remains mostly inevitable, and the disease fatal in majority patients. A major challenge treatment patients relapsed MM timely identification options personalized manner. Current approaches precision oncology aim at matching specific DNA mutations to drugs, but incorporation genome-wide RNA profiles has not yet been clinically assessed. Methods We have...
Selinexor is the first selective inhibitor of nuclear export to be approved for treatment relapsed or refractory multiple myeloma (MM). Currently, there are no known genomic biomarkers assays help select MM patients at higher likelihood response selinexor. Here, we aimed characterize transcriptomic correlates selinexor-based therapy.We performed RNA sequencing on CD138+ cells from bone marrow 100 with who participated in BOSTON study, followed by differential gene expression and pathway...
Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% median progression-free survival (PFS) 4–5 months. Previous studies explored addition weekly cyclophosphamide, but we hypothesized that daily dosing allows for better synergy. We report the open-label, single-center phase II study pomalidomide, cyclophosphamide (PCD). Thirty-three were evaluable efficacy underwent 28-day cycles (4 mg/day, D1-21), (50 mg...
Abstract Background Multiple Myeloma (MM) is a progressive plasma cell neoplasm characterized by heterogeneous clonal expansion. Despite promising response rates achieved with anti-BCMA CAR-T therapy, patients may still relapse and there are currently no clear therapeutic options in post-CAR-T settings. In this report, we present case of post-BCMA relapsed/refractory (RR) MM patient skin extramedullary disease (EMD) which novel MAPK inhibition combinatorial strategy was implemented based on...
ABSTRACT RNA editing is an epitranscriptomic modification of emerging relevance to disease development and manifestations. ADAR1, which resides on human chromosome 1q21, editor whose over-expression, either by interferon (IFN) induction or through gene amplification, associated with increased poor outcomes in Multiple Myeloma (MM). Here we explored the role ADAR1 context MM progression, focusing a group 23 patients MMRF CoMMpass Study for RNAseq WES datasets exist matched pre-and...
ABSTRACT The remarkable genetic heterogeneity of Multiple Myeloma (MM) poses a significant challenge for proper prognostication and clinical management patients. Accurate dissection the molecular landscape disease robust identification homogeneous classes patients are essential steps to reliable risk stratification development novel precision medicine strategies. Here we introduce MM-PSN, first multi-omics Patient Similarity Network newly diagnosed MM. MM-PSN has enabled three broad patient...
<p>SUPPLEMENTARY FIGURE 3: PFS1 and OS in PGV-B/C carriers vs non-carriers (combined cohort)</p>
<div>Abstract<p>First-degree relatives of patients with multiple myeloma are at increased risk for the disease, but contribution pathogenic germline variants (PGV) in hereditary cancer genes to and outcomes is not well characterized. To address this, we analyzed exomes two independent cohorts 895 786 myeloma. PGVs were identified 8.6% Discovery cohort 11.5% Replication cohort, a notable presence high- or moderate-penetrance (associated autosomal dominant predisposition) DNA...