A5035077043- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Genomics and Rare Diseases
- Quinazolinone synthesis and applications
- Chromosomal and Genetic Variations
- Eosinophilic Disorders and Syndromes
- Glycosylation and Glycoproteins Research
- Cancer Mechanisms and Therapy
- Viral-associated cancers and disorders
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Prenatal Screening and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Retinoids in leukemia and cellular processes
- Research on Leishmaniasis Studies
Mayo Clinic in Arizona
2016-2025
Mayo Clinic
2016-2024
WinnMed
2018-2024
University of Minnesota Rochester
2022
Mayo Clinic in Florida
2016-2022
University of Minnesota
2011-2021
Albert Einstein College of Medicine
2011-2021
Laboratory of Molecular Genetics
2018-2020
Institut thématique Génétique, génomique et bioinformatique
2013-2019
University of Minnesota Medical Center
2017
Risk stratification in multiple myeloma is important for prognostication, patient selection clinical trials, and comparison of treatment approaches. We developed validated a staging system that incorporates additional FISH abnormalities not included the R-ISS reflects additive effects co-occurring high-risk disease features. first evaluated prognostic value predefined cytogenetic laboratory 2556 Mayo Clinic patients diagnosed between February 2004 June 2019. then used data from 1327 to...
Abstract Cell cycle deregulation is central to the initiation and fatality of multiple myeloma, second most common hematopoietic cancer, although impaired apoptosis plays a critical role in accumulation myeloma cells bone marrow. The mechanism for intermittent, unrestrained proliferation unknown, but mutually exclusive activation cyclin-dependent kinase 4 (Cdk4)-cyclin D1 or Cdk6-cyclin D2 precedes marrow vivo. Here, we show that by specific inhibition Cdk4/6, orally active small-molecule PD...
Kleefstra syndrome, caused by haploinsufficiency of euchromatin histone methyltransferase 1 (EHMT1), is characterized intellectual disability (ID), autism spectrum disorder (ASD), characteristic facial dysmorphisms, and other variable clinical features. In addition to EHMT1 mutations, de novo variants were reported in four additional genes (MBD5, SMARCB1, NR1I3, KMT2C), single individuals with characteristics overlapping syndrome. Here, we present a novel cohort five patients loss function...
Abstract We used single cell RNA-Seq to examine molecular heterogeneity in multiple myeloma (MM) 597 CD138 positive cells from bone marrow aspirates of 15 patients at different stages disease progression. 790 genes were selected by coefficient variation (CV) method and organized into four groups (L1–L4) using unsupervised clustering. Plasma each patient clustered least two based on gene expression signature. The L1 group contained all MGUS having the lowest involved oxidative...
Abstract Cytogenetic abnormalities are found in most multiple myeloma (MM) patients. Although their prognostic value has been well studied, there limited data on the association of primary cytogenetic with disease characteristics and treatment response. This study was designed to evaluate these associations. is a retrospective including 2027 Mayo Clinic patients diagnosed MM between February 2004 2018 who had testing by FISH at diagnosis. Translocations t(4;14), t(14;16), t(6;14), t(14;20)...
Abstract A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities multiple myeloma (MM). It unclear whether +1q independently associated with decreased overall survival (OS). The objective of this study was to evaluate impact on clinical characteristics, treatment response, and outcomes. We included 1376 Mayo Clinic patients diagnosed MM from 2005 2018 who underwent fluorescence situ hybridization testing at diagnosis a panel including probe. found 391 (28%) anemia,...
Detection of hallmark genomic aberrations in acute myeloid leukemia (AML) is essential for diagnostic subtyping, prognosis, and patient management. However, cytogenetic/cytogenomic techniques used to identify those aberrations, such as karyotyping, fluorescence situ hybridization (FISH), or chromosomal microarray analysis (CMA), are limited by the need skilled personnel well significant time, cost, labor. Optical genome mapping (OGM) provides a single, cost-effective assay with significantly...
Cytogenetics has long represented a critical component in the clinical evaluation of hematologic malignancies. Chromosome banding studies provide simultaneous snapshot genome-wide copy number and structural variation, which have been shown to drive tumorigenesis, define diseases, guide treatment. Technological innovations sequencing ushered our present-day genomics era. With recent publications highlighting novel technologies as alternatives conventional cytogenetic approaches, we, an...
Abstract Decades of research into the molecular mechanisms cancer and development novel therapeutics have yielded a number remarkable successes. However, our ability to broadly assign effective, rationally targeted therapies in personalized manner remains elusive for many patients, drug resistance persists as major problem. This is part due well-documented heterogeneity cancer, including diversity tumor cell lineages states, spectrum somatic mutations, complexity microenvironments,...
Multiple myeloma is a hematologic malignancy characterized by the proliferation of neoplastic plasma cells in bone marrow. Although first-to-market proteasome inhibitor bortezomib (Velcade) has been successfully used to treat patients with myeloma, drug resistance remains an emerging problem. In this study, we identify signatures sensitivity and gene expression profiling (GEP) using pairs bortezomib-sensitive (BzS) bortezomib-resistant (BzR) cell lines created from Bcl-XL/Myc...
Abstract Multiple myeloma, the second most common hematopoietic cancer, ultimately becomes refractory to treatment when self-renewing multiple myeloma cells begin unrestrained proliferation by unknown mechanisms. Here, we show that one, but not more than of three early G1 D cyclins is elevated in each case myeloma. Cyclin D1 or D3 expression does vary clinical course, alone insufficient promote cell cycle progression unless cyclin-dependent kinase 4 (cdk4) also elevated, absence cdk6,...
Abstract Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared European (EAs). This striking disparity, one of the highest any cancer, may be due underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes MM, and it likely that disparity associated with only certain subtypes. Previous efforts understand this have relied on self-reported race rather than ancestry, which result bias. To mitigate difficulties, we...
Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess impact rearrangement on clinical characteristics, treatment response, and survival patients with myeloma.This a retrospective including 1,342 seen Mayo Clinic Rochester, MN, from January 2006 2018, who had cytogenetic testing by FISH at diagnosis, using break apart probe (8q24.1).A found 8% associated...
Abstract Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients other subtypes of AML. However, ∼40% relapse, the literature suggests that inv(16) fare differently from those t(8;21). We retrospectively analyzed 537 CBF-AML, focusing on additional cytogenetic aberrations to examine their impact clinical outcomes. Trisomies chromosomes...
Richter transformation (RT) represents the development of an aggressive lymphoma in chronic lymphocytic leukemia (CLL). Patients with RT and relapsed CLL have poor outcomes. Yet, extent molecular differences between two entities has not been fully explored. In this pilot study, we conducted RNA-seq targeted panel sequencing nodal tissues from 12 patients, including seven five CLL. Analysis data revealed major clusters, cluster C1 remaining all C2. Within C2, one ultimately developed RT; it...
Multiple myeloma (MM) is a plasma cell (PC) malignancy that preceded by monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering multiple (SMM). MGUS and SMM PCs exhibit the same primary oncogenic abnormalities as MM but lack end-organ damage defines proliferative disease, suggesting clonal in these precursor conditions could senescence or senescence-like growth arrest. Herein we identified patient-derived features found senescent were significantly increased patients...
Abstract Fluorescence in situ hybridization (FISH) is currently the gold-standard assay to detect recurrent genomic abnormalities of prognostic significance multiple myeloma (MM). Since most translocations MM involve a position effect with heterogeneous breakpoints, we hypothesize that FISH has potential miss involving these regions. We evaluated 70 bone marrow samples from patients plasma cell dyscrasia by and whole-genome mate-pair sequencing (MPseq). Thirty cases (42.9%) displayed at...
Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional (CS) provides dynamic predictions over time. This study was conducted to estimate CS at 1-8 and impact of baseline prognostic factors on in multiple myeloma (MM) patients. is a retrospective including 2556 MM patients diagnosed between 2004 2019. (t | s) defined as probability surviving t given s years. Median age 64 follow-up 6.2 median overall 7.5 The...
Acute myeloid leukemia (AML) can be subtyped based on recurrent cytogenetic and molecular genetic abnormalities with diagnostic prognostic significance. Although characterization classically involves conventional chromosome and/or fluorescence in situ hybridization (FISH) assays, limitations of these techniques include poor resolution the inability to precisely identify breakpoints.We evaluated whether an NGS-based methodology that detects structural copy number changes using mate pair...