A5038647604- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Glioma Diagnosis and Treatment
- Viral-associated cancers and disorders
- Advanced Breast Cancer Therapies
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- PI3K/AKT/mTOR signaling in cancer
- T-cell and Retrovirus Studies
- RNA regulation and disease
- vaccines and immunoinformatics approaches
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- RNA Research and Splicing
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- CNS Lymphoma Diagnosis and Treatment
Icahn School of Medicine at Mount Sinai
2015-2024
Tisch Cancer Institute
2024
Albert Einstein College of Medicine
2009-2023
Cancer Genetics (United States)
2018
Montefiore Medical Center
2012-2013
Russian Academy of Sciences
2001-2003
Institute of Theoretical and Experimental Biophysics
2000-2001
Integrative multiomics analysis of myeloma identifies 12 disease subtypes defined by specific patterns genetic alterations.
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...
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...
The mTOR pathway is constitutively activated in diffuse large B-cell lymphoma (DLBCL). inhibitors have activity DLBCL, although response rates remain low. We evaluated DLBCL cell lines with differential resistance to the inhibitor rapamycin: (i) identify gene expression profile(s) (GEP) associated rapamycin, (ii) understand mechanisms of rapamycin resistance, and (iii) compounds likely synergize inhibitor.We sought a GEP by stratification eight respect rapamycin. Then, using analysis...
Epigenetic drugs can overcome resistance to monoclonal antibodies in T-PLL and activate therapeutic targets for antibody-drug conjugates.
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...
Multiple myeloma is a fatal plasma cell neoplasm accounting for over 10,000 deaths in the United States each year. Despite new therapies, multiple remains incurable, and patients ultimately develop drug resistance succumb to disease. The response selective CDK4/6 inhibitors has been modest myeloma, potentially because of incomplete targeting other critical oncogenic kinases. As substantial number lines primary samples were found express AMPK-related protein kinase 5(ARK5), member AMPK family...
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...
Despite advances, there is an urgent need for effective therapeutics relapsed diffuse large B-cell lymphoma, particularly in elderly patients and primary central nervous system (CNS) lymphoma. Temozolomide (TMZ), oral DNA-alkylating agent routinely used the therapy of glioblastoma multiforme, active with CNS lymphoma but response rates are low. The mechanisms contributing to TMZ resistance unknown.We undertook unbiased genome-wide approach understand genomic methylation gene expression...
// Violetta V. Leshchenko 1 , Pei-Yu Kuo Zewei Jiang Marc A. Weniger 2 Jessica Overbey 3 Kieron Dunleavy 4 Wyndham H. Wilson Adrian Wiestner Samir Parekh Division of Hematology and Medical Oncology, Icahn School Medicine at Mount Sinai, New York, NY, USA Branch, National Heart, Lung Blood Institute, Institutes Health, Bethesda, MD, Department Health Science Policy, Lymphoid Malignancies Center for Cancer Research, Correspondence to: Parekh, e-mail: samir.parekh@mssm.edu Keywords: Mantle cell...
Abstract Background: Gaucher disease (GD), a hereditary condition characterized by glucocerebrosidase deficiency, results in the impaired degradation of glucocerebroside (GL1) and its deacetylated form, lyso-GL1 (LGL1). This leads to accumulation these substrates primarily bone marrow (BM), liver, spleen. Notably, individuals with GD face an increased risk plasma cell dyscrasias (PCD) approximately nine-fold. We present two compelling cases regression smoldering multiple myeloma (SMM)...
Abstract Background: Mantle cell lymphoma (MCL) is an incurable lymphoid neoplasm, comprising about 6% of all non-Hodgkin (NHL). The transcription factor SOX11 overexpressed in the majority MCL patients and linked to a more aggressive disease course poorer clinical outcomes. In MCL, naïve B cells experience continuous proliferation because dysregulation B-cell receptor (BCR) pathway. Our previously published data (Kuo et. al., Blood 2018) identified that aberrantly upregulated BCR signaling...
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...