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3 results on '"Akpa, Chidimma Agatha"'

1. Next-Generation-Sequencing of the Human B-Cell Receptor Improves Detection and Diagnosis and Enhances Disease Monitoring in Patients with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Author

Akpa, Chidimma Agatha, Husemann, Cora, Allen, Chris, von Brünneck, Ann-Christin, Ihlow, Jana, and Hummel, Michael

Subjects
*DNA sequencing, *LYMPHOID tissue, *IMMUNOSTAINING, *B cells, *IMMUNOGLOBULINS
Abstract

Mucosa-associated lymphoid tissue (MALT) lymphomas are slow-growing B-cell lymphomas mainly diagnosed in the stomach and termed gastric MALT lymphoma (G-MALT). Despite histological evaluation, immunostaining, and additional B-cell clonality analysis by fragment analysis, a clear-cut diagnosis is not feasible in all cases, especially for clinical follow-up of patients after treatment. We examined clonally rearranged immunoglobulin heavy- and light-chain gene sequences of 36 genomic DNA samples from six different patients obtained at different time points over the course of several years using the OncomineTM B-cell receptor pan-clonality next-generation sequencing (NGS) assay. Each case consisted of samples diagnosed with G-MALT and samples without evidence of lymphoma, based on histological examinations. We show a robust correlation (100%) of the results between the applied NGS method and histology-diagnosed G-MALT-positive patients. We also detected malignant clonotypes in samples where histology assessment failed to provide clear evidence of G-MALT (15 out of 19 samples). Furthermore, this method revealed malignant clonotypes much earlier in the disease course, with NGS of the immunoglobulin light chain being crucial in complementing immunoglobulin heavy-chain analysis. Hence, the value of NGS in routine lymphoma diagnostics is greatly significant and can be explored in order to provide better diagnoses and proffer the early detection of lymphoma relapse. [ABSTRACT FROM AUTHOR]

Published
2024
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3. DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations

Author

Akpa, Chidimma Agatha, Kleo, Karsten, Lenze, Dido, Oker, Elisabeth, Dimitrova, Lora, and Hummel, Michael

Subjects
B Cells, Adenosine, Cancer Treatment, Artificial Gene Amplification and Extension, Polymerase Chain Reaction, Translocation, Genetic, Hematologic Cancers and Related Disorders, White Blood Cells, Spectrum Analysis Techniques, Animal Cells, immune system diseases, hemic and lymphatic diseases, Medicine and Health Sciences, Cultured Tumor Cells, Cell Death, apoptosis, Hematology, Flow Cytometry, Burkitt Lymphoma, Oncology, Proto-Oncogene Proteins c-bcl-2, Cell Processes, Spectrophotometry, Proto-Oncogene Proteins c-bcl-6, Medicine, Lymphomas, Biological Cultures, Cytophotometry, Lymphoma, Large B-Cell, Diffuse, Cellular Types, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Research Article, Immune Cells, Science, Immunology, macromolecular substances, Research and Analysis Methods, Proto-Oncogene Proteins c-myc, Cell Line, Tumor, Genetics, Point Mutation, Humans, Enhancer of Zeste Homolog 2 Protein, Antibody-Producing Cells, Molecular Biology Techniques, Molecular Biology, Blood Cells, Burkittlymphoma, Lymphoma Cells, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, Cell Cultures, DZNep, Mutation
Abstract

Enhancer of zeste homolog 2 (EZH2) tri-methylates histone 3 at position lysine 27 (H3K27me3). Overexpression and gain-of-function mutations in EZH2 are regarded as oncogenic drivers in lymphoma and other malignancies due to the silencing of tumor suppressors and differentiation genes. EZH2 inhibition is sought to represent a good strategy for tumor therapy. In this study, we treated Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 3-deazaneplanocin-A (DZNep), an indirect EZH2 inhibitor which possesses anticancer properties both in-vitro and in-vivo. We aimed to address the impact of the lymphoma type, EZH2 mutation status, as well as MYC, BCL2 and BCL6 translocations on the sensitivity of the lymphoma cell lines to DZNep-mediated apoptosis. We show that DZNep inhibits proliferation and induces apoptosis of these cell lines independent of the type of lymphoma, the EZH2 mutation status and the MYC, BCL2 and BCL6 rearrangement status. Furthermore, DZNep induced a much stronger apoptosis in majority of these cell lines at a lower concentration, and within a shorter period when compared with EPZ-6438, a direct EZH2 inhibitor currently in phase II clinical trials. Apoptosis induction by DZNep was both concentration-dependent and time-dependent, and was associated with the inhibition of EZH2 and subsequent downregulation of H3K27me3 in DZNep-sensitive cell lines. Although EZH2, MYC, BCL2 and BCL6 are important prognostic biomarkers for lymphomas, our study shows that they poorly influence the sensitivity of lymphoma cell lines to DZNep-mediated apoptosis.

Published
2019

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