Article
Oncology
Jodie Hay, Anuradha Tarafdar, Ailsa K. Holroyd, Hothri A. Moka, Karen M. Dunn, Alzahra Alshayeb, Bryony H. Lloyd, Jennifer Cassels, Natasha Malik, Ashfia F. Khan, IengFong Sou, Jamie Lees, Hassan N. B. Almuhanna, Nagesh Kalakonda, Joseph R. Slupsky, Alison M. Michie
Summary: The expression of PKC beta facilitates leukemogenesis in chronic lymphocytic leukemia (CLL) and BCR-mediated signaling is identified as a key driver of CLL development in the PKC alpha-KR model.
Review
Oncology
Jennifer Edelmann
Summary: This article reviews the mutations of NOTCH1 in CLL and their impact on disease progression, discusses the effect of NOTCH1 mutations on treatment response, and provides insight into other alterations that may contribute to the dysregulation of NOTCH1 signaling in CLL cells.
FRONTIERS IN ONCOLOGY
(2022)
Review
Hematology
Shazia Nakhoda, Aldana Vistarop, Y. Lynn Wang
Summary: Bruton tyrosine kinase inhibitors (BTKi) have had a significant impact on the treatment of chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma. However, resistance to BTKi remains a challenge, and this review article provides an update on the key clinical data, mechanisms of resistance, and ongoing clinical investigations in CLL, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL).
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Medicine, General & Internal
Jorge Cortes, Carolina Pavlovsky, Susanne Saussele
Summary: Tyrosine-kinase inhibitors have significantly altered the natural course of chronic myeloid leukaemia, allowing some patients to approach a near-normal life expectancy. Successful treatment requires understanding the patient's treatment goals, monitoring optimal response hallmarks, timely interventions, recognition of adverse events, and management of comorbidities.
Review
Hematology
Naranie Shanmuganathan, Timothy P. Hughes
Summary: The recent approval of asciminib as a treatment option for CML patients provides clinicians with more choices for therapy. Asciminib is a highly potent BCR-ABL1 inhibitor with limited off-target effects, but its position among other available TKIs is still unclear. There are many unanswered questions about the optimal use of asciminib.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
John F. Imbery, Julia Heinzelbecker, Jenny K. Jebsen, Marc McGowan, Camilla Myklebust, Nunzio Bottini, Stephanie M. Stanford, Sigrid S. Skanland, Anders Tveita, Geir E. Tjonnfjord, Ludvig A. Munthe, Peter Szodoray, Britt Nakken
Summary: Chronic lymphocytic leukaemia (CLL) is a malignancy characterized by mature B cells. Emerging evidence shows that CLL cells proliferate in response to T-helper (Th) cells in a CD40L-dependent manner. The study demonstrates that Th cells upregulate CD45 activity in CLL cells, leading to enhanced downstream antigen receptor signaling and proliferation. The increased expression of Galectin-1 and CD43, both of which are involved in CD45 regulation, was also observed. Targeting Galectin-1 or CD43 could dampen CD45 activity and CLL cell proliferation. These findings suggest that modulation of CD45 phosphatase activity could be a potential therapeutic target in CLL.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Shenmiao Yang, Abraham M. Varghese, Nitin Sood, Carlos Chiattone, Norah O. Akinola, Xiaojun Huang, Robert Peter Gale
Summary: East Asians, Asian Indians, and Amerindians have a significantly lower incidence rate of chronic lymphocytic leukemia compared to persons of European descent, suggesting a genetic rather than environmental basis for this disparity. These populations have different genetic admixtures with archaic hominins, potentially explaining the varying CLL incidences among them, as well as differences in clinical and molecular covariates of CLL. Further research is needed to determine the exact reasons behind these population variances in CLL and other lymphomas and cancers.
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)
Article
Hematology
Chiara Cavallini, Marilisa Galasso, Elisa Dalla Pozza, Roberto Chignola, Ornella Lovato, Ilaria Dando, Maria G. Romanelli, Mauro Krampera, Giovanni Pizzolo, Massimo Donadelli, Maria T. Scupoli
Summary: The study revealed the negative regulatory effects of CD20 monoclonal antibodies and their combination with BAKi on BCR signaling and cell survival in CLL. Additionally, the combination of CD20 mAbs and BAKi significantly enhanced leukemia cell death, indicating the potential of combined therapies in CLL patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Huimin Feng, Yue Fu, Zelong Cui, Minran Zhou, Lu Zhang, Zhenxing Gao, Sai Ma, Chunyan Chen
Summary: This study shows that PHF8 is significantly increased in CML patients and inhibits cell differentiation while promoting cell proliferation. Targeting PHF8, which directly regulates BCR::ABL1 expression, may be a useful therapeutic approach for CML.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Genetics & Heredity
Qiuyi Zhang, Ying Gao, Shuchun Lin, Lynn R. Goldin, Yonghong Wang, Holly Stevenson, Daniel C. Edelman, Keith Killian, Gerald Marti, Paul S. Meltzer, Song Xiang, Neil E. Caporaso
Summary: This study investigated the DNA methylation aberrations in malignant B lymphocytes of CLL patients and identified differentially methylated positions (DMPs) and differentially methylated and expressed genes (DMEGs) associated with CLL by integrating public databases. The direction of each DMEG in CLL was observed based on DMPs in the promoter and the body region, and the methylation heterogeneity of CLL subgroups and the effect of B cell maturation on CLL were explored. The findings suggest the importance of DNA methylation in the pathogenesis of CLL and provide potential markers for diagnostic and therapeutic purposes.
FRONTIERS IN GENETICS
(2023)
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.
Article
Oncology
Carmela Ciardullo, Katarzyna Szoltysek, Peixun Zhou, Monika Pietrowska, Lukasz Marczak, Elaine Willmore, Amir Enshaei, Anna Walaszczyk, Jia Yee Ho, Vikki Rand, Scott Marshall, Andrew G. Hall, Christine J. Harrison, Meera Soundararajan, Jeyanthy Eswaran
Summary: This study investigates the clinical significance of B-cell regulators BACH2 and BCL6 in chronic lymphocytic leukaemia (CLL). The results show that low levels of BACH2 and BCL6 RNA expression are associated with shorter overall survival in CLL patients.
Article
Biochemistry & Molecular Biology
Olivera Mitrovic Ajtic, Tijana Suboticki, Milos Diklic, Dragoslava Dikic, Milica Vukotic, Teodora Dragojevic, Emilija Zivkovic, Darko Antic, Vladan Cokic
Summary: The expression of S100A proteins in chronic lymphocytic leukemia is regulated by inflammation and is associated with proliferation-related signaling pathways. Inhibition of the PI3K/AKT signaling pathway stimulates S100A4 gene expression, while IL-6 stimulates the expression of S100A4 and S100A8 proteins. IL-10, on the other hand, reduces the expression of S100A8, S100A9, and S100A12 proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Hematology
Jerald Radich
Summary: Most cancer cases occur in low resource areas, where diagnosis and treatment can be especially challenging. Unique partnerships between non-profit organizations and pharmaceutical companies provide free drugs to CML patients worldwide, but performing molecular diagnostics in areas with unreliable electricity remains a major obstacle.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)