Letter
Oncology
Andrea G. S. Pepper, Antonella Zucchetto, Kevin Norris, Erika Tissino, Jerry Polesel, Zarni Soe, David Allsup, Anna Hockaday, Pei Loo Ow, Peter Hillmen, Andrew Rawstron, Daniel Catovsky, Pietro Bulian, Riccardo Bomben, Duncan M. Baird, Christopher D. Fegan, Valter Gattei, Chris Pepper
Letter
Hematology
David John Allsup, Zoe Craig, David Cairns, Dena Howard, Anna Hockaday, Adrian Bloor, Zarni Soe, Christopher Pepper, Valter Gattei, Antonella Zucchetto, Pauline Robbe, Ruth Clifford, Anna Schuh, Talha Munir, Andrew Rawstron, Peter Hillmen
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kez Cleal, Duncan M. Baird
Summary: Structural variation (SV) is important in genome evolution and disease, and Dysgu is a tool that accurately detects SVs using paired-end or long-read sequencing, with high sensitivity and fast running speed.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Hematology
Marwan Kwok, Tatjana Stankovic
Summary: In this issue of Blood, Huber et al present the results of an important prospective clinical trial, showing that the combination of obinutuzumab, ibrutinib, and venetoclax produces high rates of undetectable measurable residual disease and remarkable 2-year progression-free survival in previously untreated del(17p) or TP53-mutated chronic lymphocytic leukemia (CLL) patients.
Article
Multidisciplinary Sciences
Martin A. M. Reijns, David A. Parry, Thomas C. Williams, Ferran Nadeu, Rebecca L. Hindshaw, Diana O. Rios Szwed, Michael D. Nicholson, Paula Carroll, Shelagh Boyle, Romina Royo, Alex J. Cornish, Hang Xiang, Kate Ridout, Anna Schuh, Konrad Aden, Claire Palles, Elias Campo, Tatjana Stankovic, Martin S. Taylor, Andrew P. Jackson
Summary: Transcription-associated mutagenesis plays an important role in human genome mutations. This study reveals an ID4 mutation signature associated with the activity of topoisomerase 1 (TOP1), which causes insertions and deletions in cancer and physiological settings.
Article
Oncology
Thomas A. Burley, Andrew Hesketh, Giselda Bucca, Emma Kennedy, Eleni E. Ladikou, Benjamin P. Towler, Simon Mitchell, Colin P. Smith, Christopher Fegan, Rosalynd Johnston, Andrea Pepper, Chris Pepper
Summary: The study revealed the role of the FAK signaling pathway in CLL cell migration and tissue invasion by investigating the mechanisms underlying CLL cell migration. Inhibition of FAK effectively reduced CLL cell migration and invasion, suggesting the potential for combining FAK inhibition with current targeted therapies to enhance CLL treatment efficacy.
Editorial Material
Hematology
Tatjana Stankovic, Marwan Kwok
Letter
Oncology
Romina Royo, Laura Magnano, Julio Delgado, Sara Ruiz-Gil, Josep Ll. Gelpi, Holger Heyn, Malcom A. Taylor, Tatjana Stankovic, Xose S. Puente, Ferran Nadeu, Elias Campo
BLOOD CANCER JOURNAL
(2022)
Article
Genetics & Heredity
Helene E. B. Geiller, Adam Harvey, Rhiannon E. Jones, Julia W. Grimstead, Kez Cleal, Eric A. Hendrickson, Duncan M. Baird
Summary: Telomerase activity is the main telomere maintenance mechanism in human cancers, but 15% of cancers use a recombination-based mechanism called ALT. Loss of ATRX gene and telomere dysfunction during crisis can initiate the ALT pathway and confer replicative immortality to cells.
Review
Oncology
Alice O'Donnell, Chris Pepper, Simon Mitchell, Andrea Pepper
Summary: Chronic lymphocytic leukemia (CLL) is a common and incurable type of leukemia. The Nuclear Factor-Kappa B (NF-kappa B) transcription factor plays a role in CLL, with high levels associated with disease progression and drug resistance. Genetic mutations and microenvironmental factors activate NF-kappa B through two distinct pathways, leading to tumor cell survival and resistance to treatment. Understanding how the CLL microenvironment drives NF-kappa B activation is crucial for developing new therapeutic approaches.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Eleanor Jayawant, Arran Pack, Heather Clark, Emma Kennedy, Ankur Ghodke, John Jones, Chris Pepper, Andrea Pepper, Simon Mitchell
Summary: A new flow cytometry-based analysis technique, NF-kappa B fingerprinting, reveals the heterogeneity of NF-kappa B composition in DLBCL, which is not captured by commonly used cell-of-origin classifications. Computational modeling predicts that RelA is a key determinant of DLBCL's response to microenvironmental stimuli, and substantial variability in RelA is identified within ABC-DLBCL cell lines. Incorporating NF-kappa B fingerprints and mutational information into computational models enables the prediction of heterogeneous DLBCL cell populations' responses to microenvironmental stimuli, and these predictions are experimentally validated.
FRONTIERS IN ONCOLOGY
(2023)
Article
Mathematical & Computational Biology
Ielyaas Cloete, Victoria M. Smith, Ross A. Jackson, Andrea Pepper, Chris Pepper, Meike Vogler, Martin J. S. Dyer, Simon Mitchell
Summary: In healthy cells, the balance between pro- and anti-apoptotic BCL2 family proteins is maintained, but this balance is frequently disrupted in cancer cells, resulting in overexpression of anti-apoptotic BCL2 family proteins. This variability in protein expression and sequestration contributes to different response to BH3-mimetics in Diffuse Large B Cell Lymphoma (DLBCL). By using computational systems biology, we can accurately predict the sensitivity of DLBCL cells to BH3-mimetics, which can be explained by cell-to-cell variability in the abundances of signaling proteins. These models can also predict synergistic combinations of BH3-mimetics and guide personalized treatment approaches in B cell malignancies.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2023)
Editorial Material
Hematology
Marwan Kwok, Tatjana Stankovic
Summary: The study demonstrates the continued robust clinical activity of the triplet combination of obinutuzumab, ibrutinib, and venetoclax in previously untreated CLL patients with del(17p) and/or TP53 mutations.
Article
Genetics & Heredity
Philip Bland, Harry Saville, Patty T. Wai, Lucinda Curnow, Gareth Muirhead, Jadwiga Nieminuszczy, Nivedita Ravindran, Marie Beatrix John, Somaieh Hedayat, Holly E. Barker, James Wright, Lu Yu, Ioanna Mavrommati, Abigail Read, Barrie Peck, Mark Allen, Patrycja Gazinska, Helen N. Pemberton, Aditi Gulati, Sarah Nash, Farzana Noor, Naomi Guppy, Ioannis Roxanis, Guy Pratt, Ceri Oldreive, Tatjana Stankovic, Samantha Barlow, Helen Kalirai, Sarah E. Coupland, Ronan Broderick, Samar Alsafadi, Alexandre Houy, Marc-Henri Stern, Stephen Pettit, Jyoti S. Choudhary, Syed Haider, Wojciech Niedzwiedz, Christopher J. Lord, Rachael Natrajan
Summary: SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1(MUT)) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling. SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing.
Article
Oncology
Evan A. Mulligan, Susan J. Tudhope, Jill E. Hunter, Arabella E. G. Clift, Sarah L. Elliott, Geoffrey P. Summerfield, Jonathan Wallis, Chris J. Pepper, Barabara Durkacz, Stephany Veuger, Elaine Willmore
Summary: This study demonstrates the importance of RelB in CLL, as high basal levels of RelB DNA binding correlate with nuclear RelB protein expression and are associated with poor clinical outcomes. CD40L stimulation promotes RelB activation and CLL cell proliferation. Inhibiting non-canonical NF-kappa B signalling may be a novel therapeutic approach for CLL.
