A5007955482- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Chronic Myeloid Leukemia Treatments
- Hematopoietic Stem Cell Transplantation
- Retinoids in leukemia and cellular processes
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Gastrointestinal disorders and treatments
- Single-cell and spatial transcriptomics
- Cutaneous lymphoproliferative disorders research
- Integrated Circuits and Semiconductor Failure Analysis
- Nanoparticle-Based Drug Delivery
- Biopolymer Synthesis and Applications
- Cancer Cells and Metastasis
- Esophageal and GI Pathology
Cornell University
2016-2024
Weill Cornell Medicine
2018-2024
University of Pennsylvania
2011-2019
Keio University
2004
Abstract Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem (LSC). To validate this hypothesis vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenografts (PDX) with cytarabine (AraC). AraC residual AML neither immature, nor LSCs. Strikingly, AraC-resistant preexisting and persisting displayed high levels of reactive oxygen species, showed increased mitochondrial mass,...
Significance Rapid evolution of drug resistance associated with secondary kinase domain (KD) mutations is the best characterized mechanism acquired to effective tyrosine inhibitor (TKI) therapy. Medicinal chemistry efforts have largely been devoted toward synthesizing type II TKIs that, by targeting an inactive conformation, are believed afford greater selectivity than I that bind active conformation. The only previously described TKI ability successfully suppress all resistance-conferring...
Acute myeloid leukemia (AML) is a disease with high incidence of relapse that originated and maintained from stem cells (LSCs). Hematopoietic can be distinguished LSCs by an array cell surface antigens such as CD123, thus candidate to eliminate using variety approaches, including CAR T cells. Here, we evaluate the potential allogeneic gene-edited targeting CD123 (UCART123). UCART123 are TCRαβneg generated healthy donors TALEN® gene-editing technology, decreasing likelihood graft vs host...
Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 differentially expressed on the surface BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 investigational product consisting allogeneic T cells expressing anti-CD123 chimeric antigen (CAR), edited TALEN ® nucleases. In this study, we...
Abstract Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved the treatment of various + hematological malignancies. While CAR induce objective responses in majority patients, relapse frequently occurs upon loss expression by neoplastic cells. Radiation therapy (RT) has been successfully employed circumvent targets preclinical models pancreatic cancer. At least part, this reflects ability RT elicit death (DR) malignant cells, enabling at...
Activating mutations in Fms-like tyrosine kinase 3 (FLT3) occur ∼30% of adult cases acute myeloid leukemia (AML). Selective second- and third-generation FLT3 inhibitors have shown significant clinical activity patients with relapsed FLT3-mutant AML. However, clearance clones does not consistently occur, disease will progress most after an initial response. This scenario challenges the model AML being oncogene addicted, it suggests that redundant signaling pathways regulate cell survival...
Abstract The epichaperome is a new cancer target composed of hyperconnected networks chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to inhibitors. We developed flow cytometry-based assay for evaluation and monitoring abundance at the single level, goal prospectively identifying patients likely respond inhibitors, measure engagement, dependency during treatment. As proof principle, we describe patient unclassified...
The c-Myb and GATA-3 transcription factors play important roles in T cell development. We recently reported that c-Myb, GATA-3, Menin form a core complex regulates expression ultimately Th2 development human peripheral blood cells. However, for cytokine were not demonstrated. In this article, we report cooperatively an essential role IL-13 though direct binding to conserved response element (CGRE), enhancer expression. shown activate the CGRE-IL-13 promoter by ∼160-fold, mutation of...
Summary Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia‐propagating population and are thought to be cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements warranted facilitate accurate risk stratification. Previously, we published composition a one‐tube flow cytometric assay, characterised by presence 13 important membrane markers for detection. Here present validation experiments assay several large AML research centres,...
Sixteen months after a cord blood stem cell transplantation, 6-year-old girl was diagnosed with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD). A CT scan revealed nodules in both lungs, but the patient had neither lymphadenopathy nor other lesions. The diagnosis confirmed by histopathologic evaluation and increased level of EBV DNA peripheral blood. successfully treated rituximab, complete regression tumors achieved. This case reveals need to include...
Pneumatosis cystoides intestinalis (PCI) is a rare complication after hematopoietic stem cell transplantation that characterized by multiple intramural gas collections in the bowel wall (1,2). PCI also has been associated with chronic obstructive lung disease, collagen diseases, necrotizing enterocolitis premature infants, intestinal infections, ischemic disorders, and immunosuppressive drug therapy (3). The pathogenesis of unknown. Mechanical, bacterial, mucosal damage are most commonly...