Nikhil C. Munshi
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View article: Distinct populations of vascular smooth muscle and sinoatrial progenitors are localized adjacent to pro-epicardium
Distinct populations of vascular smooth muscle and sinoatrial progenitors are localized adjacent to pro-epicardium Open
The developmental potential of cells adjacent to pro-epicardial (PE) cells (pro-EpiCs) that also express pro-EpiC markers is unknown. We apply single-cell mRNA deep sequencing paired with RNAScope validation, bioinformatic analysis, and li…
View article: The impact of Duffy genotype on progression-free survival (PFS) with lenalidomide, Bortezomib, and dexamethasone (RVd) alone or RVd plus autologous stem cell transplantation (ASCT) and continuous R maintenance in patients (pts) with newly diagnosed multiple myeloma (NDMM): Updated subgroup analysis of the phase 3 DETERMINATION trial
The impact of Duffy genotype on progression-free survival (PFS) with lenalidomide, Bortezomib, and dexamethasone (RVd) alone or RVd plus autologous stem cell transplantation (ASCT) and continuous R maintenance in patients (pts) with newly diagnosed multiple myeloma (NDMM): Updated subgroup analysis of the phase 3 DETERMINATION trial Open
Background: A single nucleotide polymorphism (SNP) in ACKR1/DARC results in erythrocyte Duffy null phenotype in ~66% of African American (AA) and <1% of White pts. This is associated with lower absolute neutrophil count (ANC) and has a key…
View article: Single-cell transcriptomics of AL amyloidosis reveals pathogenic mechanisms, immune interactions and altered clonal and polyclonal plasma cell phenotypes
Single-cell transcriptomics of AL amyloidosis reveals pathogenic mechanisms, immune interactions and altered clonal and polyclonal plasma cell phenotypes Open
Background: Systemic light chain (AL) amyloidosis is caused by clonal expansion of plasma cells (PCs) secreting misfolded monoclonal immunoglobulin that aggregate in tissues, leading to organ dysfunction. While recent studies have begun to…
View article: Spatial proteomics of the bone marrow reveals distinct Tumor–Immune niches in smoldering and relapsed myeloma and their remodeling in response to bispecific antibody and CAR-T therapy
Spatial proteomics of the bone marrow reveals distinct Tumor–Immune niches in smoldering and relapsed myeloma and their remodeling in response to bispecific antibody and CAR-T therapy Open
INTRODUCTION T cell–redirecting therapies, including CAR T cells and bispecific antibodies (BsAbs), have transformed the treatment of relapsed/refractory multiple myeloma (RRMM) and are being explored in earlier stages, including high-risk…
View article: Retrospective real-world data analysis of morbidity burden and healthcare costs in idiopathic multicentric castleman disease compared with matched controls (BURDEN-iMCD)
Retrospective real-world data analysis of morbidity burden and healthcare costs in idiopathic multicentric castleman disease compared with matched controls (BURDEN-iMCD) Open
Introduction: Idiopathic multicentric Castleman disease (iMCD) is a rare, cytokine-driven hematologic disorder characterized by diffuse lymphadenopathy and systemic inflammation. Prior studies have suggested increased rates of hematologic …
ID2 Suppresses Multiple Myeloma Cell Proliferation by Repressing the Activity of the Transcription Factor TCF3 Open
Transcription factors and their cofactors are major and selective nononcogene dependencies in multiple myeloma cells. By performing a gain-of-function perturbation screen in human multiple myeloma cell lines, we identified the inhibitor of…
View article: The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma
The endogenous T cell landscape is reshaped by CAR-T cell therapy and predicts treatment response in multiple myeloma Open
While most patients initially respond to CAR-T cell treatment, responses often are not durable and subsequent lines of immunotherapy show diminishing success. In this study, we investigated the co-evolutionary dynamics between CAR-T cells …
View article: Potentially Inappropriate Medications, Frailty, and Outcomes in Patients With Cancer Managed in a National Health Care System
Potentially Inappropriate Medications, Frailty, and Outcomes in Patients With Cancer Managed in a National Health Care System Open
Background: Previous studies have operationalized the NCCN list of high-risk medications in older adults into a measurable tool known as the Geriatric Oncology Potentially Inappropriate Medications (GO-PIMs) scale. The current study aims t…
View article: Distinct patient, tumour and chimeric antigen receptor T‐cell characteristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed and refractory multiple myeloma
Distinct patient, tumour and chimeric antigen receptor T‐cell characteristics are associated with initiating versus sustaining responses to idecabtagene vicleucel in relapsed and refractory multiple myeloma Open
Summary Idecabtagene vicleucel (ide‐cel), a B‐cell maturation antigen (BCMA)‐directed autologous chimeric antigen receptor (CAR) T‐cell therapy, was studied in relapsed and refractory multiple myeloma after >4 prior lines of therapy in Kar…
View article: Bedaquiline Amplifies Proteasome Inhibitor Efficacy and Overcomes Resistance in Multiple Myeloma
Bedaquiline Amplifies Proteasome Inhibitor Efficacy and Overcomes Resistance in Multiple Myeloma Open
Proteasome inhibitors (PIs) are cornerstone therapies for multiple myeloma (MM), yet resistance remains a major barrier to durable responses. To identify druggable vulnerabilities that enhance PIs efficacy, we performed a small-molecule ch…
View article: Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia
Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia Open
Patients with multiple myeloma (MM) and Waldenström macroglobulinemia (WM) have increased risk of severe coronavirus disease 2019. Impaired humoral responses to the primary vaccination series against severe acute respiratory syndrome coron…
View article: Supplementary Figure S1 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Supplementary Figure S1 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Supplementary Figure S1. Expression profiling and correlation analysis of MYC and ACC1 in patients with newly diagnosed multiple myeloma (NDMM).
View article: Supplementary Figure S5 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Supplementary Figure S5 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Supplementary Figure S5. Gene set enrichment analysis in MM cells following ND-646 treatment, and evaluation of cell growth under combined treatment with ND-646 and simvastatin.
View article: Data from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Data from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Purpose:In multiple myeloma, tumor cells reprogram metabolic pathways to sustain growth and monoclonal immunoglobulin production. This study examines acetyl-CoA carboxylase 1 (ACC1), the enzyme driving the rate-limiting step in de novo lip…
View article: Supplementary Figure S2 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Supplementary Figure S2 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Supplementary Figure S2. Quantitative analysis of ACACA expression in multiple myeloma (MM) cell lines.
View article: Supplementary Figure S4 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Supplementary Figure S4 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Supplementary Figure S4. Impact of pharmacological inhibition (ND-630 and ND-646) and ACC1 knockdown on MM cell viability, proliferation, and de novo lipogenesis (DNL) rates in MYC overexpressed MM cells.
View article: Supplementary Figure S3 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Supplementary Figure S3 from Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Supplementary Figure S3. Representative western blot analysis showing protein levels of ACC1, phosphorylated ACC (pACC), and MYC in MM cells.
View article: The Evolution and Subtypes of Waldenstrom Macroglobulinemia: Findings from a Multi-omic Analysis of 249 Treatment Naive MYD88L265P Mutated Patients.
The Evolution and Subtypes of Waldenstrom Macroglobulinemia: Findings from a Multi-omic Analysis of 249 Treatment Naive MYD88L265P Mutated Patients. Open
To study the heterogeneity of transcriptional and genomic traits that underlie the clinical presentation of untreated Waldenstrom’s Macroglobulinemia (WM), we performed multi-omic studies in 249 treatment-naive patients with WM. For all pa…
View article: Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma
Targeting Acetyl-CoA Carboxylase Suppresses <i>De Novo</i> Lipogenesis and Tumor Cell Growth in Multiple Myeloma Open
Purpose: In multiple myeloma, tumor cells reprogram metabolic pathways to sustain growth and monoclonal immunoglobulin production. This study examines acetyl-CoA carboxylase 1 (ACC1), the enzyme driving the rate-limiting step in de novo li…
Development of hyperdiploidy starts at an early age and takes a decade to complete Open
Nearly half of patients with multiple myeloma (MM) have hyperdiploidy (HMM) at diagnosis. Although HMM occurs early, the mutational processes before and after hyperdiploidy are still unclear. Here, we used 72 whole-genome sequencing sample…
View article: A Novel Ribonuclease Targeting Small Molecule RNA-Degrader (MYC-RiboTAC) Overcomes MYC Dependency in Multiple Myeloma
A Novel Ribonuclease Targeting Small Molecule RNA-Degrader (MYC-RiboTAC) Overcomes MYC Dependency in Multiple Myeloma Open
c-MYC (MYC) is an important oncogene in multiple myeloma (MM), driving MM cell proliferation, metabolism, and survival. However, MYC has been challenging to therapeutically target because of its protein structure lacking well-defined bindi…
View article: Uncovering the Tumor Antigen Landscape in Patients Undergoing Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance Treatment
Uncovering the Tumor Antigen Landscape in Patients Undergoing Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance Treatment Open
Backgroun d: Identifying novel antigenic targets for immune-based therapy in Multiple Myeloma (MM) is a critical area of investigation. The BMT CTN 1401 (NCT02728102), a national randomized trial evaluating dendritic cell (DC)/MM fusion ce…
View article: Development of Novel Peripheral Blood Count-Based Prognostic Index for Multiple Myeloma
Development of Novel Peripheral Blood Count-Based Prognostic Index for Multiple Myeloma Open
In multiple myeloma (MM), clonal plasma cells evade immune surveillance and proliferate within an inflammatory bone marrow microenvironment. During pathogenesis, monocyte-derived tumor-associated macrophages help myeloma cells to avoid apo…
View article: <i>Discovery of Undocumented, Cancer-Specific and Pro-Inflammatory Isoforms of WNK2 That Are Highly Expressed in MYD88 Mutated Waldenström's Macroglobulinemia and Represent Novel Therapeutic Targets.</i>
<i>Discovery of Undocumented, Cancer-Specific and Pro-Inflammatory Isoforms of WNK2 That Are Highly Expressed in MYD88 Mutated Waldenström's Macroglobulinemia and Represent Novel Therapeutic Targets.</i> Open
The genomic landscape of WM is characterized by mutations in MYD88 (MYD88MUT) and CXCR4 in 95-97% and 30-40% of patients, respectively. Transgenic mouse studies suggest that MYD88MUT alone is insufficient for lymphomagenesis and that addit…
View article: Early Safety and Efficacy of CAR-T Cell Therapy in Precursor Myeloma: Results of the CAR-PRISM Study Using Ciltacabtagene Autoleucel in High-Risk Smoldering Myeloma
Early Safety and Efficacy of CAR-T Cell Therapy in Precursor Myeloma: Results of the CAR-PRISM Study Using Ciltacabtagene Autoleucel in High-Risk Smoldering Myeloma Open
Introduction: CAR-T cell therapy has been used in relapsed multiple myeloma (MM) with deep and durable responses but some patients still eventually relapse. We hypothesized that the use of Ciltacabtagene Autoleucel (cilta-cel), a BCMA-dire…
View article: Phase II Trial of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma
Phase II Trial of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma Open
Background: Daratumumab, bortezomib, lenalidomide and dexamethasone (D-RVD) has shown high rates of minimal residual disease (MRD) negativity and clinical benefit in newly-diagnosed multiple myeloma (MM) and is now a standard of care regim…
View article: Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma
Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma Open
Bone marrow microenvironment plays an important role in promoting growth and survival of multiple myeloma (MM) cells. The tumor-promoting immune microenvironment is augmented while antitumor immune responses are inhibited. Although clinica…