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
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
Health Care Sciences & Services
Adi Zoref-Lorenz, Mona Yuklea, Guy Topaz, Michael B. Jordan, Martin Ellis
Summary: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can occur in hematologic malignancies. This case report highlights the challenges of diagnosing and managing HLH in patients with stable chronic lymphocytic leukemia. The patient developed severe complications and ultimately died despite treatment.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2022)
Article
Medicine, General & Internal
Barbara Eichhorst, Carsten U. Niemann, Arnon P. Kater, Moritz Fuerstenau, Julia von Tresckow, Can Zhang, Sandra Robrecht, Michael Gregor, Gunnar Juliusson, Patrick Thornton, Philipp B. Staber, Tamar Tadmor, Vesa Lindstrom, Caspar da Cunha-Bang, Christof Schneider, Christian B. Poulsen, Thomas Illmer, Bjoern Schoettker, Thomas Noesslinger, Ann Janssens, Ilse Christiansen, Michael Baumann, Henrik Frederiksen, Marjolein van der Klift, Ulrich Jaeger, Maria B. L. Leys, Mels Hoogendoorn, Kourosh Lotfi, Holger Hebart, Tobias Gaska, Harry Koene, Lisbeth Enggaard, Jereon Goede, Josien C. Regelink, Anouk Widmer, Florian Simon, Nisha De Silva, Anna-Maria Fink, Jasmin Bahlo, Kirsten Fischer, Clemens-Martin Wendtner, Karl A. Kreuzer, Matthias Ritgen, Monika Brueggemann, Eugen Tausch, Mark-David Levin, Marinus van Oers, Christian Geisler, Stephan Stilgenbauer, Michael Hallek
Summary: In fit patients with CLL, venetoclax-obinutuzumab, with or without ibrutinib, showed superior results compared to chemoimmunotherapy as a first-line treatment, with higher rates of undetectable minimal residual disease and progression-free survival.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
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
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Article
Hematology
Fabienne Meier-Abt, Junyan Lu, Ester Cannizzaro, Marcel F. Pohly, Sandra Kummer, Sibylle Pfammatter, Laura Kunz, Ben C. Collins, Ferran Nadeu, Kwang Seok Lee, Peng Xue, Myriam Gwerder, Michael Roiss, Jennifer Huellein, Sebastian Scheinost, Sascha Dietrich, Elias Campo, Wolfgang Huber, Ruedi Aebersold, Thorsten Zenz
Summary: This study uncovered mutations affecting protein expression in CLL and identified signaling pathways associated with trisomy 12. STAT2 protein expression was linked to specific drug responses, providing a protein expression reference map for CLL.
Article
Cell Biology
Vanessa Villegas-Ruiz, Antonio Romo-Mancillas, Isabel Medina-Vera, Kattia Alejandra Castro-Lopez, Josselene Carina Ramirez-Chiquito, Marco Antonio Fonseca-Montano, Mercedes Edna Garcia-Cruz, Roberto Rivera-Luna, Julieta Griselda Mendoza-Torreblanca, Sergio Juarez-Mendez
Summary: Leukemia is a common childhood malignancy in Mexico with low treatment success rate. The study found that there are multiple transcript variants of the proliferating cell nuclear antigen (PCNA) gene, and some of these variants are expressed at significantly low levels in acute lymphoblastic leukemia patients, which could serve as potential molecular markers for relapse.
Article
Oncology
David Allard, Pavel Chrobak, Yacine Bareche, Bertrand Allard, Priscilla Tessier, Marjorie A. Bergeron, Nathalie A. Johnson, John Stagg
Summary: Our study identified CD73 as a pro-leukemic immune checkpoint in CLL and uncovered a previously unknown sex bias for the CD73-adenosine pathway. The therapeutic potential of targeting CD73 in CLL was investigated using genetically engineered mice, revealing a pro-leukemic role for CD73 in an autochthonous mouse model of CLL. Our findings suggest that targeting CD73 in CLL in combination with anti-PD-1/PD-L1 immunotherapies may be beneficial, with sex potentially contributing to responses to adenosine-targeting agents.
Article
Medicine, General & Internal
Katarzyna Skorka, Paulina Wlasiuk, Agnieszka Karczmarczyk, Krzysztof Giannopoulos
Summary: Functional TLRs play a role in modulating anti-tumor effects, but excessive expression may promote tumor progression. MYD88 and TLRs exhibit correlations in CLL patients compared to healthy volunteers, with potential implications for treatment timing.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Oncology
Yu Nie, Xiaoya Yun, Ya Zhang, Xin Wang
Summary: Metabolic reprogramming plays a vital role in the initiation and progression of chronic lymphocytic leukemia (CLL). This review summarizes the critical metabolic processes in CLL and discusses the regulation of metabolism by cells in the microenvironment and oncogenes/tumor suppressor regulators. Targeting metabolic enzymes or signal pathways may impede the progression of CLL.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Immunology
Pedram Mahmoudi Aliabadi, Ruth Teuber, Peter K. K. Jani, Landon Wilson, Philipp Enghard, Stephen Barnes, Nicholas Chiorazzi, Andreas Radbruch, Fritz Melchers, Hiromi Kubagawa
Summary: Fc mu R is a member of the FcR family that is selectively expressed in lymphocytes and differs from other FcRs expressed by immune and non-hematopoietic cells. Studies have shown that Fc mu R has a regulatory function in B-cell tolerance and that its elevated levels are associated with chronic lymphocytic leukemia.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Shenmiao Yang, Xiaojun Huang, Robert Peter Gale
Summary: Transplantation has been used to treat chronic lymphocytic leukemia for over 35 years, but is only considered for less than 1% of highly selected patients. While some patients may achieve long-term leukemia-free survival with transplants, they also come with significant morbidity and mortality. The anti-leukemia effects of transplants are influenced by various factors, including drugs, radiation, and immune mechanisms.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Cell Biology
Cristina Bagacean, Cristina Adela Iuga, Anne Bordron, Adrian Tempescul, Ioana-Ecaterina Pralea, Delphine Bernard, Melanie Cornen, Tiffany Bergot, Christelle Le Dantec, Wesley Brooks, Hussam Saad, Jean-Christophe Ianotto, Jacques-Olivier Pers, Mihnea Zdrenghea, Christian Berthou, Yves Renaudineau
Summary: Chronic lymphocytic leukemia (CLL) is characterized by significant biologic and clinical heterogeneity. This study investigated the proteomic profiles of CLL B-cells, showing differences between stable and progressive disease groups at an early stage, with RNA splicing dysregulation underlying CLL evolution and impacting B-cell survival and migration.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Review
Medicine, General & Internal
Mazyar Shadman
Summary: Chronic lymphocytic leukemia is an immunocompromised blood cancer that can be treated with targeted agents like BTK inhibitors or BCL2 inhibitors, but currently there is no cure for the disease.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)