A5066964026- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Childhood Cancer Survivors' Quality of Life
- Lymphoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Pharmaceutical studies and practices
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Cancer therapeutics and mechanisms
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Genomics and Rare Diseases
- Glycosylation and Glycoproteins Research
- Virus-based gene therapy research
- PI3K/AKT/mTOR signaling in cancer
- Neutropenia and Cancer Infections
Children's Hospital of Philadelphia
2016-2025
University of Pennsylvania
2016-2025
Philadelphia University
2016-2025
Princess Máxima Center
2024-2025
Abramson Cancer Center
2014-2023
California University of Pennsylvania
2023
UPMC Hillman Cancer Center
2021
Penn Center for AIDS Research
2021
Pediatrics and Genetics
2020
University of Cincinnati
2020
Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR–ABL1–positive ALL, alterations lymphoid transcription factor genes, and poor outcome. The frequency spectrum genetic in Ph-like ALL its responsiveness tyrosine kinase inhibition are undefined, especially adolescents adults.
Pediatric acute lymphoblastic leukemia (ALL) is a heterogeneous disease consisting of distinct clinical and biological subtypes that are characterized by specific chromosomal abnormalities or gene mutations. Mutation genes encoding tyrosine kinases uncommon in ALL, with the exception Philadelphia chromosome-positive where t(9,22)(q34;q11) translocation encodes constitutively active BCR-ABL1 kinase. We recently identified poor prognostic subgroup pediatric BCR-ABL1-negative ALL patients...
Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability predict groups of types cancer that will respond immune targeting remains limited. This study dissected complexity architecture AML at high resolution assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts children adults we defined...
Allogeneic chimeric antigen receptor T-cell (CART) therapies require multiple gene edits to be clinically tractable. Most allogeneic CARTs have been created using editing techniques that induce DNA double-stranded breaks (DSBs), resulting in unintended on-target outcomes with potentially unforeseen consequences. Cytosine base editors (CBEs) install C•G T•A point mutations T cells, between 90% and 99% efficiency silence expression without creating DSBs, greatly reducing or eliminating...
Background Ruxolitinib, an orally bioavailable JAK1/JAK2 inhibitor, may treat cancers with CRLF2 and/or JAK pathway mutations. Procedure A phase 1 trial of ruxolitinib was performed to determine the maximum tolerated or recommended 2 dose, dose-limiting toxicities (DLTs), pharmacokinetics (PK), and pharmacodynamics (PD) in children recurrent/refractory solid tumors (STs). Ruxolitinib administered twice daily (BID) 28-day cycles at five dose levels (15, 21, 29, 39, 50 mg/m2/dose). PK PD...
Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, approach was single-gene or focused multigene testing, but centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report laboratory validation clinical utility a large cohort NGS somatic results diagnosis, prognosis, treatment wide range Subjects were accrued retrospectively at single quaternary-care hospital. Sequence analyses performed on 367...
Background. Immune exhaustion and senescence are dominant dysfunctional states of effector T cells major hurdles for the success cancer immunotherapy. In current study, we characterized how acute myeloid leukemia (AML) promotes generation senescent-like CD8+ whether they have prognostic relevance.
Background Successful development of chimeric antigen receptor (CAR) T cell immunotherapy for children and adults with relapsed/refractory acute myeloid leukemia (AML) is highly desired given their poor clinical prognosis frequent inability to achieve cure conventional chemotherapy. Initial experiences CD19 CAR patients B-cell malignancies highlighted the critical impact intracellular costimulatory domain selection (CD28 vs 4-1BB (CD137)) on expansion in vivo persistence that may outcomes....
Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 validated tumor in multiple myeloma (MM) acute lymphoblastic leukemia (T-ALL) also overexpressed myeloid (AML). Here, we developed human CD38-redirected (CART-38) as unified treat 3 different occur across...
Aberrant skipping of coding exons in CD19 and CD22 compromises the response to immunotherapy B-cell malignancies. Here, we showed that MS4A1 gene encoding human CD20 also produces several messenger RNA (mRNA) isoforms with distinct 5' untranslated regions. Four variants (V1-4) were detected using sequencing (RNA-seq) at stages normal differentiation B-lymphoid malignancies, V1 V3 being most abundant. During activation Epstein-Barr virus infection, redirection splicing from coincided...