Andrea Pepper

Andrea Pepper
Brighton and Sussex Medical School | BSMS

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20
Publications
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219
Citations

Publications

Publications (20)
Article
Full-text available
Pathogenesis in chronic lymphocytic leukemia (CLL) is strongly linked to the potential for leukemic cells to migrate to and proliferate within lymph-nodes. Previous in vivo studies suggest that all leukemic cells participate in cycles of migration and proliferation. In vitro studies, however, have shown heterogeneous migration patterns. To investig...
Article
Full-text available
The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibitio...
Article
CLL remains incurable despite BCR-targeted inhibitors revolutionizing treatment. This suggests that other signaling molecules are involved in disease escape mechanisms and resistance. Toll-like receptor 9 (TLR9) is a promising candidate, which is activated by unmethylated CpG-DNA. Here, we show that plasma from CLL patients contains significantly m...
Article
Background - Although there has been a revolution in the treatment of chronic lymphocytic leukemia (CLL), the challenge remains to identify the right drugs for the right patients. It is widely accepted that CIT, including the 'gold standard' fludarabine, cyclophosphamide and rituximab (FCR), is contraindicated for patients with TP53 disruption and,...
Article
Full-text available
Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are incurable hematological malignancies that are pathologically linked with aberrant NF-κB activation. In this study, we identified a group of novel C8-linked benzofused Pyrrolo[2,1-c][1,4]benzodiazepines (PBD) monomeric hybrids capable of sequence-selective inhibition of NF-κB with low...
Article
Acute myeloid leukaemia (AML) is the most common adult acute leukaemia with the lowest survival rate. It is characterised by a build‐up of immature myeloid cells anchored in the protective niche of the bone marrow (BM) microenvironment. The CXCL12/CXCR4 axis is central to the pathogenesis of AML as it has fundamental control over AML cell adhesion...
Article
Full-text available
Purpose of review: Acute myeloid leukaemia (AML) is a heterogeneous malignancy for which treatment options remain suboptimal. It is clear that a greater understanding of the biology of the AML niche will enable new therapeutic strategies to be developed in order to improve treatment outcomes for patients. Recent findings: Recent evidence has hig...
Article
Despite the success of autologous anti-CD19 CAR T cell therapy in B-Acute lymphoblastic leukaemia (B-ALL) and Diffuse Large B Cell Lymphoma (DLBCL), treatment failures occur. One contributing factor may be the intrinsic T cell fitness of the CAR T cell product that is influenced by the underlying malignancy and prior treatments. With the advent of...
Article
Full-text available
CD4+ T-follicular helper cells are essential for the survival, proliferation, and differentiation of germinal center B-cells and have been implicated in the pathogenesis of follicular lymphoma. To further define the role of these cells in follicular lymphoma, we used multiparameter confocal microscopy to compare the architecture of normal and neopl...
Poster
Full-text available
Acute Myeloid Leukaemia(AML) is an aggressive blood cancer affecting both children and adults. It is caused by failure in myeloid precursor cell differentiation into functional granulocytes resulting in accumulation of immature/ineffective leukaemic cells in the bone marrow (BM). Normal haemopoiesis fails and patients suffer infections, bleeding an...
Article
Full-text available
Acetylsalicylic acid, or aspirin, is one of the most common non-steroidal anti-inflammatory drugs, which has been shown to have anti-cancer effects. However, high doses are needed making it unsuitable as an oncology agent. We have previously reported increased potency in a series of hydroxybenzoate zinc (HBZn) aspirin analogues. Here we show that 3...
Article
Full-text available
Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a powerful tool in achieving a complete remission in a range of B-cell malignancies, most notably B-acute lymphoblastic leukaemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). However, there are limitations, including inability to manufacture CAR-T cells from the patient’s...
Article
Full-text available
Key Points Basal intracellular Ca2+ levels and migration increase with higher CD38 expression in CLL cells. Rap1 and the Rap1 guanine-nucleotide exchange factor RasGRP2 are required for CLL migration and regulated by CD38 levels.
Article
Full-text available
B-cell receptor activation, occurring within lymph nodes, plays a key role in the pathogenesis of chronic lymphocytic leukemia and is linked to prognosis. As well as activation of downstream signaling, receptor ligation triggers internalization, transit to acidified endosomes and degradation of ligand-receptor complexes. In the present study we inv...

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