Samantha L. Savage
A5074989124- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Multiple Myeloma Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- Fungal Plant Pathogen Control
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Chromatin Remodeling and Cancer
- Eosinophilic Disorders and Syndromes
- RNA Research and Splicing
- Histone Deacetylase Inhibitors Research
- Cell Adhesion Molecules Research
- Genetics and Neurodevelopmental Disorders
- Advanced Biosensing Techniques and Applications
- Kruppel-like factors research
Oregon Health & Science University
2013-2024
OHSU Knight Cancer Institute
2014
Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity genomic, transcriptomic, and clinical annotations for large cohort AML patients, which facilitated discovery functional genomic correlates. Here, we present dataset that has been harmonized our initial report to yield cumulative 805 patients (942 specimens). show strong cross-cohort concordance identify features response. Further, deconvoluting...
Abstract Although the use of ATP-competitive tyrosine kinase inhibitors oncoprotein BCR-ABL1 has enabled durable responses in patients with chronic myeloid leukemia (CML), issues drug resistance and residual leukemic stem cells remain. To test whether degradation could offer improved response, we developed a series proteolysis-targeting chimera (PROTAC) that allosterically target protein recruit E3 ligase Von Hippel-Lindau, resulting ubiquitination subsequent oncogenic fusion protein. In...
FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit heavily pretreated relapsed/refractory patients, responses transient relapse eventually occurs. Here, to investigate the mechanisms of resistance, we perform whole exome sequencing patient samples...
Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations agents will be required to treat these diseases effectively. Combinatorial approaches also critical for combating emergence genetically heterogeneous subclones, rescue signals...
Abstract Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, those involving epigenetic dysregulation, remain largely elusive, hampering clinical management this malignancy. To identify novel druggable targets, we carried out unbiased high-throughput chemical screening observed that NPC cells were highly sensitive to inhibitors cyclin-dependent kinases (CDK), especially THZ1, a covalent...
Colony-stimulating factor-3 receptor (
Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in the majority of chronic neutrophilic leukemia (CNL) and a smaller percentage atypical myeloid (aCML) cases. Although CSF3R point (e.g., T618I) are emerging as key players CNL/aCML, significance rarer is unknown. In this study, we assess importance T640N mutation marker CNL/aCML potential therapeutic target.Sanger sequencing samples was performed to identify CNL aCML. The oncogenicity relative T618I assessed by...
// Paula de Melo Campos 1 , João A. Machado-Neto Christopher Eide 2, 3 Samantha L. Savage 2 Renata Scopim-Ribeiro 1, 5 Adriana da Silva Souza Duarte Patricia Favaro 4 Irene Lorand-Metze Fernando F. Costa Cristina E. Tognon Brian J. Druker Sara T. Olalla Saad Fabiola Traina Hematology and Hemotherapy Center - University of Campinas/Hemocentro Unicamp, Instituto Nacional Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil Knight Cancer Institute, Oregon Health & Science University,...
Abstract Purpose: Chronic neutrophilic leukemia (CNL), chronic myelomonocytic (CMML), atypical myeloid (aCML), and unclassified myeloproliferative neoplasms (MPN-U) are a group of heterogeneous disorders belonging to rare entities or myelodysplastic/myeloproliferative (MDS/MPN) syndromes. Due lack specific molecular markers the limited understanding pathogenesis, treatment these diseases remains empirical, resulting in poor outcomes. Recently, recurrent mutations ASXL1, TET2, SRSF2 cell...
Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity genomic, transcriptomic, and clinical annotations for large cohort AML patients, which facilitated discovery functional genomic correlates. Here, we present new dataset, has been harmonized our initial report to yield cumulative 805 patients (942 specimens). show strong cross-cohort validation identify features response. Further, deconvoluting...
The Philadelphia chromosome (Ph) resulting from the t(9;22) translocation generates oncogenic BCR::ABL1 fusion protein that is most commonly associated with chronic myeloid leukemia (CML) and Ph-positive (Ph+) acute lymphoblastic (ALL). There are also rare instances of patients (≤1%) newly diagnosed (AML) harbor this (Paietta et al., Leukemia12: 1881 [1998]; Keung Leuk Res28: 579 [2004]; Soupir Am J Clin Pathol127: 642 [2007]). AML BCR::ABL has only recently been provisionally classified by...
Abstract We have recently discovered that a large percentage (59%) of patients with chronic neutrophilic leukemia (CNL) or atypical myeloid (aCML) mutations in Colony Stimulating Factor 3 Receptor (CSF3R, aka GCSFR) (Maxson et al, NEJM 2013). These are either point the extracellular domain (T618I, T615A) truncations cytoplasmic domain. The most frequent mutation is T618I (aka T595I). two classes CSF3R operate through distinct mechanisms result differential sensitivity to inhibition tyrosine...