Article
Biology
Irene Lopez-Oreja, Andre Gohr, Heribert Playa-Albinyana, Ariadna Giro, Fabian Arenas, Morihiro Higashi, Rupal Tripathi, Monica Lopez-Guerra, Manuel Irimia, Marta Aymerich, Juan Valcarcel, Sophie Bonnal, Dolors Colomer
Summary: In this study, the researchers used deep RNA sequencing data to analyze CLL tumor samples and SF3B1 wild-type and K700E-mutated CLL cell lines. They identified protein pre-mRNA features and cryptic 39 splice site events associated with SF3B1 mutation. They also demonstrated the cytotoxic effects of the splicing modulator H3B-8800 in CLL samples and SF3B1-mutated cell lines, and its potential therapeutic use in combination with the BCL2 inhibitor venetoclax in CLL.
LIFE SCIENCE ALLIANCE
(2023)
Article
Genetics & Heredity
Binyamin A. Knisbacher, Ziao Lin, Cynthia K. Hahn, Ferran Nadeu, Marti Duran-Ferrer, Kristen E. Stevenson, Eugen Tausch, Julio Delgado, Alex Barbera-Mourelle, Amaro Taylor-Weiner, Pablo Bousquets-Munoz, Ander Diaz-Navarro, Andrew Dunford, Shankara Anand, Helene Kretzmer, Jesus Gutierrez-Abril, Sara Lopez-Tamargo, Stacey M. Fernandes, Clare Sun, Mariela Sivina, Laura Z. Rassenti, Christof Schneider, Shuqiang Li, Laxmi Parida, Alexander Meissner, Francois Aguet, Jan A. Burger, Adrian Wiestner, Thomas J. Kipps, Jennifer R. Brown, Michael Hallek, Chip Stewart, Donna S. Neuberg, Jose Martin-Subero, Xose S. Puente, Stephan Stilgenbauer, Catherine J. Wu, Elias Campo, Gad Getz
Summary: This study identifies genetic drivers and molecular subtypes associated with clinical outcomes in chronic lymphocytic leukemia (CLL) through genomic, transcriptomic, and epigenomic analysis. The findings provide fresh insights into the oncogenesis and prognostication of CLL.
Article
Biochemistry & Molecular Biology
Kristan V. Piroeva, Charlotte Mcdonald, Charalampos Xanthopoulos, Chelsea Fox, Christopher T. Clarkson, Jan-Philipp Mallm, Yevhen Vainshtein, Luminita Ruje, Lara C. Klett, Stephan Stilgenbauer, Daniel Mertens, Efterpi Kostareli, Karsten Rippe, Vladimir B. Teif
Summary: This study compared the nucleosome positions in chronic lymphocytic leukemia (CLL) patients and healthy individuals, and found significant changes in nucleosome positioning in CLL. The spacing between nucleosomes was shortened, and changes in nucleosome occupancy were linked to chromatin remodeling and reduced DNA methylation. Nucleosome positioning can be used to classify CLL subtypes and monitor disease progression.
Article
Oncology
Giuseppa De Luca, Giannamaria Cerruti, Sonia Lastraioli, Romana Conte, Adalberto Ibatici, Nikki Di Felice, Fortunato Morabito, Paola Monti, Gilberto Fronza, Serena Matis, Monica Colombo, Sonia Fabris, Alessia Ciarrocchi, Antonino Neri, Paola Menichini, Manlio Ferrarini, Paolo Nozza, Franco Fais, Giovanna Cutrona, Mariella Dono
Summary: The use of Next Generation Sequencing (NGS) in CLL patients revealed a high frequency of subclonal TP53 mutations. Precise identification of these mutations during the disease is necessary to prevent treatment failures.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Erhan Aptullahoglu, Jonathan P. Wallis, Helen Marr, Scott Marshall, Nick Bown, Elaine Willmore, John Lunec
Summary: Chronic lymphocytic leukemia (CLL) is a genetically and clinically heterogeneous malignancy affecting older individuals. Novel targeted therapies are needed for CLL patients who are treatment resistant or relapse. This study found that SF3B1 mutations were associated with poor response to the MDM2 inhibitor RG7388 in CLL patients. Patients with wild-type SF3B1 and TP53 are more likely to benefit from treatment with MDM2 inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Clare Sun, Chen Yun-Ching, Aina Martinez Zurita, Maria Joao Baptista, Stefania Pittaluga, Delong Liu, Daniel Rosebrock, Satyen Harish Gohil, Nakhle S. Saba, Theresa Davies-Hill, Sarah E. M. Herman, Gad Getz, Mehdi Pirooznia, Catherine J. Wu, Adrian Wiestner
Summary: In CLL, oncogenic processes are upregulated in the lymph nodes and in cases with unmutated IGHV region. Single-cell RNA sequencing reveals 3 major cell states in CLL: quiescent, activated, and proliferating. Activated tumor cells are associated with inferior treatment-free survival and the presence of activated CD4+ memory T cells and M2 macrophages in the lymph nodes. Clonal evolution occurs in approximately half of the patients, but is not associated with AICDA expression. However, a T-cell inflamed microenvironment in the lymph nodes is associated with clonal stability.
Article
Multidisciplinary Sciences
Monika Szelest, Marta Masternak, Malgorzata Zajac, Michal Chojnacki, Katarzyna Skorka, Joanna Zaleska, Agnieszka Karczmarczyk, Grazyna Stasiak, Ewa Wawrzyniak, Aleksandra Kotkowska, Monika Siemieniuk-Rys, Joanna Purkot, Edyta Subocz, Edyta Cichocka, Waldemar Tomczak, Daria Zawirska, Krzysztof Giannopoulos
Summary: This study aims to evaluate the impact of NOTCH1 mutation on MYC and NPM1 expression in CLL cells and explore the relationship between these mutations and CLL prognostic markers.
Review
Oncology
Billy Michael Chelliah Jebaraj, Stephan Stilgenbauer
Summary: Telomeres play a crucial role in chronic lymphocytic leukemia (CLL), with their dysfunction shaping the disease progression. Members of the shelterin complex and TERT activation are closely associated with CLL cell survival and proliferation.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Larry Mansouri, Birna Thorvaldsdottir, Lesley-Ann Sutton, Georgios Karakatsoulis, Manja Meggendorfer, Helen Parker, Ferran Nadeu, Christian Brieghel, Stamatia Laidou, Riccardo Moia, Davide Rossi, Mark Catherwood, Jana Kotaskova, Julio Delgado, Ana E. Rodriguez-Vicente, Rocio Benito, Gian Matteo Rigolin, Silvia Bonfiglio, Lydia Scarfo, Mattias Mattsson, Zadie Davis, Ajay Gogia, Lata Rani, Panagiotis Baliakas, Hassan Foroughi-Asl, Cecilia Jylha, Aron Skaftason, Inmaculada Rapado, Fatima Miras, Joaquin Martinez-Lopez, Javier de la Serna, Jesus Maria Hernandez Rivas, Patrick Thornton, Maria Jose Larrayoz, Maria Jose Calasanz, Viktoria Fesus, Zoltan Matrai, Csaba Bodor, Karin E. Smedby, Blanca Espinet, Anna Puiggros, Ritu Gupta, Lars Bullinger, Francesc Bosch, Barbara Tazon-Vega, Fanny Baran-Marszak, David Oscier, Florence N'Guyen-Khac, Thorsten Zenz, Maria Jose Terol, Antonio Cuneo, Maria Hernandez-Sanchez, Sarka Pospisilova, Ken Mills, Gianluca Gaidano, Carsten U. Niemann, Elias Campo, Jonathan C. Strefford, Paolo Ghia, Kostas Stamatopoulos, Richard Rosenquist
Summary: Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. This study assessed the impact of nine recurrently mutated genes in 4580 CLL patients and found that mutations in all genes except MYD88 were associated with significantly shorter time-to-first-treatment. The findings highlight the importance of a compartmentalized approach in identifying high-risk patients, particularly among those with mutated IGHV.
Article
Hematology
Giovanni Del Poeta, Annalisa Biagi, Luca Laurenti, Annalisa Chiarenza, Federico Pozzo, Idanna Innocenti, Massimiliano Postorino, Francesca Maria Rossi, Maria Ilaria Del Principe, Riccardo Bomben, Paolo de Fabritiis, Antonio Bruno, Maria Cantonetti, Francesco Di Raimondo, Antonella Zucchetto, Valter Gattei
Summary: NOTCH1 mutations are associated with poorer response to ibrutinib treatment in chronic lymphocytic leukemia patients, leading to shorter progression free survival and overall survival.
Article
Biochemical Research Methods
Thomas Cokelaer, Sarah Cohen-Boulakia, Frederic Lemoine
Summary: Improving reproducibility in bioinformatics data analysis is crucial and various tools have been developed for this purpose, but their adoption still needs to be increased. Integrating reproducibility into bioinformatics Master's programs is the most effective way to make it a standard practice in data analysis projects.
Review
Oncology
Pablo Oppezzo, Marcelo Navarrete, Nicholas Chiorazzi
Summary: This review article discusses the dual role of the enzyme activation-induced cytidine deaminase (AID) in adaptive immunity and B-cell malignancies, emphasizing its pathological effects as a causative factor in leukemia and lymphomas. It summarizes the expression and function of AID in normal B lymphocytes, evaluates potential causes for AID expression in leukemic cells, and discusses its role in lymphomagenesis based on recent genomic landscape analyses of leukemia and lymphomas. The review also touches upon the correlation between AID off-target mutations and tumor-gene drivers in these cancers, and how these mutations could impact disease progression.
FRONTIERS IN ONCOLOGY
(2021)
Review
Hematology
Adi Nagler, Catherine J. Wu
Summary: Single-cell analysis has revolutionized the systematic analysis of complex cell populations like cancers. It has rapidly evolved from processing a few cells to handling hundreds of thousands at a time. This technique provides detailed genetic, transcriptomic, epigenomic, and spatial information at the single-cell level, leading to deeper insights into molecular disease subtypes and cellular circuitry. In the case of chronic lymphocytic leukemia (CLL), single-cell analysis has already revealed new knowledge about the disease progression, impact of novel therapies, and interactions with nonmalignant immune cells.
Article
Genetics & Heredity
Pauline Robbe, Kate E. Ridout, Dimitrios V. Vavoulis, Helene Dreau, Ben Kinnersley, Nicholas Denny, Daniel Chubb, Niamh Appleby, Anthony Cutts, Alex J. Cornish, Laura Lopez-Pascua, Ruth Clifford, Adam Burns, Basile Stamatopoulos, Maite Cabes, Reem Alsolami, Pavlos Antoniou, Melanie Oates, Doriane Cavalieri, Genomics England Research Consortium, Cll Pilot Consortium, Jane Gibson, Anika Prabhu, Ron Schwessinger, Daisy Jennings, Terena James, Uma Maheswari, Marti Duran-Ferrer, Piero Carninci, Samantha J. L. Knight, Robert Mansson, Jim Hughes, James Davies, Mark Ross, David Bentley, Jonathan C. Strefford, Stephen Devereux, Andrew R. Pettitt, Peter Hillmen, Mark J. Caulfield, Richard S. Houlston, Jose Martin-Subero, Anna Schuh
Summary: This study reports the whole-genome sequencing of 485 chronic lymphocytic leukemia patients and identifies a range of recurrent coding and noncoding genetic mutations. The study also provides a high-resolution map of structural variants, copy number changes, and global genome features, and demonstrates the relationship of these features with clinical outcomes.
Review
Oncology
Florence Nguyen-Khac
Summary: Although the 17p deletion is rare in treatment-naive CLL, its frequency is higher in refractory/relapsed CLL, especially in patients undergoing chemotherapy. TP53 disruption is the strongest prognostic factor for chemotherapy resistance, and the use of Bruton tyrosine kinase inhibitors and BCL2 inhibitors is recommended. Rare cases of CLL may also have translocation or gain of the MYC oncogene, and double-hit CLL (with del(17p) and MYC gain) has a very poor prognosis. The prognostic impact of TP53 disruption with MYC aberrations in patients receiving targeted therapies needs to be evaluated.
FRONTIERS IN ONCOLOGY
(2022)
