A5028206160- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Neutropenia and Cancer Infections
- Fungal Infections and Studies
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- Antifungal resistance and susceptibility
- Protein Degradation and Inhibitors
- Advanced Biosensing Techniques and Applications
- Hematopoietic Stem Cell Transplantation
- Chromatin Remodeling and Cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Multiple Myeloma Research and Treatments
- CRISPR and Genetic Engineering
- Acute Lymphoblastic Leukemia research
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Lysosomal Storage Disorders Research
- Clinical Reasoning and Diagnostic Skills
- Systemic Lupus Erythematosus Research
Dana-Farber Cancer Institute
2017-2024
Harvard University
2015-2023
Brigham and Women's Hospital
2015
Tufts University
2013
Boston University
2010-2011
Abstract Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted the discovery LZTR1 as an adapter a Cullin-3 RING E3 ubiquitin ligase complex responsible degradation RAS GTPases. In parallel, dysregulated expression via aberrant splicing mutations was identified clonal hematopoietic conditions. Here we identify that loss LZTR1, or leukemia-associated mutants substrate GTPase RIT1 escape degradation, drives stem cell (HSC) expansion vivo. Although...
CD123, a subunit of the interleukin-3 receptor, is expressed on ∼80% acute myeloid leukemias (AMLs). Tagraxofusp (TAG), recombinant fused to truncated diphtheria toxin payload, first-in-class drug targeting CD123 approved for treatment blastic plasmacytoid dendritic cell neoplasm. We previously found that AMLs with acquired resistance TAG were re-sensitized by DNA hypomethylating agent azacitidine (AZA) and TAG-exposed cells became more dependent antiapoptotic molecule BCL-2. Here, we report...
Polycomb repressive epigenetic complexes are recurrently dysregulated in cancer. Unlike polycomb complex 2 (PRC2), the role of PRC1 oncogenesis and therapy resistance is not well-defined. Here, we demonstrate that highly recurrent mutations subunits BCOR BCORL1 leukemia disrupt assembly a noncanonical PRC1.1 complex, thereby selectively unlinking RING-PCGF enzymatic core from chromatin-targeting auxiliary subcomplex. As result, BCOR-mutated localized to chromatin but lacks activity, leading...
Antifungal prophylaxis (AFP) is recommended for acute myeloid leukemia (AML) patients receiving the combination of venetoclax (VEN) and a hypomethylating agent (HMA), but benefit this practice unclear. We identified 131 with newly diagnosed AML who received frontline VEN/HMA evaluated use AFP its association invasive fungal infections (IFIs) outcomes. Seventeen percent our at any time. Overall incidence IFI ('possible,' 'probable,' or 'proven' infection, as defined by European Mycoses Study...
Bleeding in patients with acute myeloid leukemia (AML) receiving intensive induction chemotherapy is multifactorial and contributes to early death. We sought define the incidence risk factors of grade 4 bleeding support strategies for mitigation. events were retrospectively assessed between day-14 day +60 treatment according World Health Organization (WHO) assessment scale, which includes as fatal, life-threatening, retinal visual impairment, or involving central nervous system. Predictors...
Optical interference is a powerful technique for monitoring surface topography or refractive index changes in thin film layer. Reflectance spectroscopy provides label-free biosensing capability by small variations signature resulting from optical path length surface-adsorbed biomolecules. Spectral reflectance data can be acquired either broad wavelength illumination and at single point, thus necessitating scanning, varying the of imaging reflected intensity allowing acquisition spectral...
Abstract Invasive fungal disease (IFD) can be a severe treatment complication in patients with myeloid malignancies, but current risk models do not incorporate disease-specific factors, such as somatic gene mutations. Germline GATA2 deficiency is associated susceptibility to IFD. To determine whether mutations were IFD risk, we identified 2 complementary cohorts of malignancy, based on (1) the diagnosis invasive aspergillosis (IA), or (2) presence during standard clinical sequencing. We...
<div>Abstract<p>Polycomb repressive epigenetic complexes are recurrently dysregulated in cancer. Unlike polycomb complex 2 (PRC2), the role of PRC1 oncogenesis and therapy resistance is not well-defined. Here, we demonstrate that highly recurrent mutations subunits <i>BCOR</i> <i>BCORL1</i> leukemia disrupt assembly a noncanonical PRC1.1 complex, thereby selectively unlinking RING-PCGF enzymatic core from chromatin-targeting auxiliary subcomplex. As...
Supplementary Figure from <i>BCOR</i> and <i>BCORL1</i> Mutations Drive Epigenetic Reprogramming Oncogenic Signaling by Unlinking PRC1.1 Target Genes
Supplementary Data from <i>BCOR</i> and <i>BCORL1</i> Mutations Drive Epigenetic Reprogramming Oncogenic Signaling by Unlinking PRC1.1 Target Genes
<div>Abstract<p>Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted the discovery LZTR1 as an adapter a Cullin-3 RING E3 ubiquitin ligase complex responsible degradation RAS GTPases. In parallel, dysregulated expression via aberrant splicing mutations was identified clonal hematopoietic conditions. Here we identify that loss LZTR1, or leukemia-associated mutants substrate GTPase RIT1 escape degradation, drives stem cell (HSC)...
<div>Abstract<p>Polycomb repressive epigenetic complexes are recurrently dysregulated in cancer. Unlike polycomb complex 2 (PRC2), the role of PRC1 oncogenesis and therapy resistance is not well-defined. Here, we demonstrate that highly recurrent mutations subunits <i>BCOR</i> <i>BCORL1</i> leukemia disrupt assembly a noncanonical PRC1.1 complex, thereby selectively unlinking RING-PCGF enzymatic core from chromatin-targeting auxiliary subcomplex. As...