A5054895103- DNA Repair Mechanisms
- Lymphoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- PARP inhibition in cancer therapy
- Chronic Lymphocytic Leukemia Research
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Viral-associated cancers and disorders
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cutaneous lymphoproliferative disorders research
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Virus-based gene therapy research
- CNS Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Biochemical and Molecular Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Stress Responses and Cortisol
- Multiple Myeloma Research and Treatments
- Renal and related cancers
- Cancer Genomics and Diagnostics
Fox Chase Cancer Center
2019-2024
Temple University Health System
2019-2024
University of Pennsylvania
2016-2023
Temple University
2020-2022
The University of Texas MD Anderson Cancer Center
2017-2019
University of Tennessee Health Science Center
2013-2016
Center for Cancer Research
2013
University of Tennessee at Knoxville
2013
The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or yielded new information regarding factors prognostic importance, are intended aid physicians decision-making. These Insights focus recent select updates Guidelines, including familial genetic alterations AML, postinduction postremission strategies low-risk acute promyelocytic leukemia...
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of blasts in peripheral blood, bone marrow, and/or other tissues. It most common form acute among adults and accounts for largest number annual deaths from leukemias United States. Like AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN) malignancy. rare aggressive proliferation precursors cells that frequently involves skin, central nervous system, organs This discussion...
The aim of this study was to examine tumor-infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy.Intratumoral CD4, CD8, FOXP3 were examined by immunohistochemistry using a computer-assisted quantitative analysis 136 PDAC who received therapy pancreaticoduodenectomy. results correlated clinicopathological parameters survival.High CD4 TILs treated associated high CD8 (P = 0.003), differentiation 0.04),...
We conducted a phase I/II multicenter trial using 6 cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment patients CD30-positive (+) B-cell lymphomas. Thirty-one were evaluable toxicity 29 efficacy including 22 primary mediastinal lymphoma (PMBCL), 5 diffuse large (DLBCL), 2 gray zone (GZL). There no treatment-related deaths; 32% had non-hematological grade 3/4 toxicities. The overall response rate was 100% (95%...
Abstract Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using combination therapy have produced remarkable results in terms rate complete remission frequency undetectable minimal residual disease. However, laboratory rationale behind success drug still lacking. A better understanding how these two synergize...
For many years, skin was just thought of as a barrier to protect against variety insults from the external environment. Our body’s largest organ is gradually revealing itself be complex o...
Burkitt lymphoma/leukemia cells carry t(8;14)(q24;q32) chromosomal translocation encoding IGH/MYC, which results in the constitutive expression of MYC oncogene. Here, it is demonstrated that untreated and cytarabine (AraC)-treated IGH/MYC-positive lymphoma accumulate a high number potentially lethal DNA double-strand breaks (DSB) display low levels BRCA2 tumor suppressor protein, key element homologous recombination (HR)-mediated DSB repair. deficiency was associated with diminished HR...
Synthetic lethality triggered by PARP inhibitor (PARPi) yields promising therapeutic results. Unfortunately, tumor cells acquire PARPi resistance, which is usually associated with the restoration of homologous recombination, loss PARP1 expression, and/or DNA double-strand break (DSB) end resection regulation. Here, we identify a constitutive mechanism resistance to PARPi. We report that bone marrow microenvironment (BMM) facilitates DSB repair activity in leukemia protect them against...
Acute myeloid leukemia (AML) is an aggressive malignancy that requires rapid treatment with chemotherapies to reduce tumor burden. However, these can compromise lymphocyte function, thereby hindering normal anti-tumor immune responses and likely limiting the efficacy of subsequent immunotherapy. To better understand negative impacts, we assessed immunological effects standard-of-care AML therapies on phenotype function over time. When compared healthy donors, untreated patients showed...
To report findings from the 2021 Society for Hematopathology/European Association Haematopathology Workshop within category of B-cell lineage neoplasms' transdifferentiation into histiocytic/dendritic cell neoplasms (HDCNs).The workshop panel reviewed 29 cases, assigned consensus diagnoses, and summarized findings.The specific diagnoses transdifferentiated HDCN tumors were histiocytic sarcoma (16); Langerhans histiocytosis/sarcoma (5); indeterminate DC tumor (1); HDCN, unclassifiable (1)....
Session 2 of the 2021 Society for Hematopathology and European Association Haematopathology Workshop collected examples lineage infidelity transdifferentiation in B-lineage neoplasms, including after targeted therapy.Twenty cases were submitted. Whole-exome sequencing genome-wide RNA expression analysis available on a limited subsample.A diagnosis B-cell acute lymphoblastic leukemia (B-ALL) was rendered at least 1 biopsy from 13 patients. There case myeloid (AML); remaining 6 mature...
More than 70% of Epstein-Barr virus (EBV)-negative Hodgkin lymphoma (HL) cases display inactivation TNFAIP3 (A20), a ubiquitin-editing protein that regulates nonproteolytic ubiquitination, indicating the significance ubiquitination in HL pathogenesis. However, precise mechanistic roles A20 and system remain largely unknown this disease. Here, we performed high-throughput CRISPR screening using ubiquitin regulator-focused single-guide RNA library lines carrying either wild-type or mutant A20....
Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have poor outcomes despite intensive chemotherapy, underscoring the need for novel therapeutic approaches. The expression status of PD1/PD-L1 in BPDCN remains unknown. We evaluated by immunohistochemistry and RNAseq profiling a cohort patients. study group included 28 patients median age 66.8 years (range, 22.8–86.7), 22 men 6 women. PD-L1 was detected 10/21 (47.6%) cases. had H-score 157. ≥60 7 protein levels (H-score) were...
Session 3 of the 2021 Workshop Society for Hematopathology/European Association Haematopathology examined progression and transformation chronic lymphocytic leukemia/small lymphoma (CLL/SLL) B-cell prolymphocytic leukemia (B-PLL).
The 2021 Society for Hematopathology and European Association Haematopathology Workshop addressed the molecular cytogenetic underpinnings of transformation transdifferentiation in lymphoid neoplasms.
DNA polymerase theta (Polθ, encoded by POLQ gene) plays an essential role in Polθ-mediated end-joining (TMEJ) of double-strand breaks (DSB). Inhibition Polθ is synthetic lethal homologous recombination (HR)-deficient tumor cells. However, DSBs can be also repaired PARP1 and RAD52-mediated mechanisms. Because leukemia cells accumulate spontaneous DSBs, we tested if simultaneous targeting or RAD52 enhance the effect HR-deficient Transformation potential oncogenes inducing BRCA1/2-deficiency...
While normal B- and T-lymphocytes require antigenic ligands to become activated via their T-cell receptors (BCR TCR, respectively), lymphomas show the broad spectrum of cell activation mechanisms regarding dependence on BCR or TCR signaling, including loss such dependence. These are generally better understood characterized for B-cell than lymphomas. some lymphomas, particularly indolent, low-grade ones remain antigen-driven, other retain antigen seemingly in an antigen-independent manner...
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy associated with various combinations of gene mutations, epigenetic abnormalities, and chromosome rearrangement-related fusions. Despite the significant degree heterogeneity in its pathogenesis, many fusions point mutations are recurrent AML have been employed risk stratification over last several decades. Gene long recognized for understanding tumorigenesis their proven roles clinical diagnosis targeted therapies....