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Yonglu Che, Curtis Chong, Marketa Limova, Laura Morris, Sunil Arani Reddy, Anne Lynn S Chang
No abstract text is available yet for this article.
April 2024: JAAD Case Reports
#22
JOURNAL ARTICLE
Jessica Bordini, Chiara Lenzi, Michela Frenquelli, Alessia Morabito, Athanasios Pseftogas, Daniela Belloni, Larry Mansouri, George Tsiolas, Eleonora Perotta, Pamela Ranghetti, Francesca Gandini, Francesca Genova, Daniel Hägerstrand, Georgios Gavriilidis, Sofoklis Keisaris, Nikolaos Pechlivanis, Frederic Davi, Neil E Kay, Anton W Langerak, Sarka Pospisilova, Lydia Scarfò, Antonios Makris, Fotis E Psomopoulos, Kostas Stamatopoulos, Richard Rosenquist, Alessandro Campanella, Paolo Ghia
The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-κB activity and disease expansion...
April 4, 2024: Leukemia
#23
JOURNAL ARTICLE
Kyoko Hayakawa, Yan Zhou, Susan A Shinton
Human old aged unmutated chronic lymphocytic leukemia U-CLL are the TCL1+ ZAP70+ CD5+ B cells. Since CD5 makes the BCR signaling tolerance, ZAP70 increased in U-CLL not only TCL1+ alone. In mice, TCL1 (TCL1A) is the negative from neonate to old aged, as TC- . VH 8-12/Vk 21-5 is the anti-thymocyte/Thy-1 autoreactive ATA B cell. When ATA μκTg generation in mice, ATA B cells are the neonate generated CD5+ B cells in B-1, and in the middle age, CD5+ can be down or continuously CD5+ , then, old aged CLL/lymphoma generation with increased CD11b in TC- ZAP70- CD5- or TC- ZAP70+ CD5+ ...
April 3, 2024: Immunity & Ageing: I & A
#24
JOURNAL ARTICLE
Minkyo Song, Barry I Graubard, Erikka Loftfield, Charles S Rabkin, Eric A Engels
BACKGROUND: The peripheral white blood cell (WBC) and neutrophil-to-lymphocyte ratio (NLR) reflect levels of inflammation and adaptive immunity. They are associated with cancer prognosis, but their associations with cancer incidence are not established. METHODS: We evaluated 443,540 cancer-free adults in the UK Biobank with data on total WBC and its subsets, follow-up starting one year after baseline. Cox regression was used to estimate hazard ratios (HRs) per quartile of WBC or NLR for incidence of 73 cancer types...
April 3, 2024: Cancer Epidemiology, Biomarkers & Prevention
#25
JOURNAL ARTICLE
Michèle Rouleau, Lyne Villeneuve, Eric P Allain, Jules McCabe-Leroux, Sophie Tremblay, Flora Nguyen Van Long, Ashwini Uchil, Charles Joly-Beauparlant, Arnaud Droit, Chantal Guillemette
BACKGROUND: High expression of the glycosyltransferase UGT2B17 represents an independent adverse prognostic marker in chronic lymphocytic leukemia (CLL). It also constitutes a predictive marker for therapeutic response and a drug resistance mechanism. The key determinants driving expression of the UGT2B17 gene in normal and leukemic B-cells remain undefined. The UGT2B17 transcriptome is complex and is comprised of at least 10 alternative transcripts, identified by previous RNA-sequencing of liver and intestine...
April 2, 2024: BMC Cancer
#26
JOURNAL ARTICLE
Salem H Alshemmari, Mazyad Almazyad, Ahmed Alsarraf, Anita Kunhikrishnan, Asha M Isaac, Andy Kaempf
INTRODUCTION: The variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis. METHODS: We involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E)...
March 22, 2024: Hematology/oncology and Stem Cell Therapy
#27
JOURNAL ARTICLE
Menna Al-Adl, Magdy M Youssef, Ahmed El-Sebaie, Sherif Refaat, Afaf El-Said
Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy...
2024: Oncology Research
#28
Gage S Black, Xiaomeng Huang, Yi Qiao, Philip Moos, Deepa Sampath, Deborah M Stephens, Jennifer A Woyach, Gabor T Marth
Bruton's tyrosine kinase (BTK) inhibitors are effective for the treatment of chronic lymphocytic leukemia (CLL) due to BTK's role in B cell survival and proliferation. Treatment resistance is most commonly caused by the emergence of the hallmark BTK C481S mutation that inhibits drug binding. In this study, we aimed to investigate whether the presence of additional CLL driver mutations in cancer subclones harboring a BTK C481S mutation accelerates subclone expansion. In addition, we sought to determine whether BTK- mutated subclones exhibit distinct transcriptomic behavior when compared to other cancer subclones...
March 16, 2024: bioRxiv
#29
JOURNAL ARTICLE
Julien Scaviner, Cristina Bagacean, Berthou Christian, Yves Renaudineau, Olivier Mignen, Souleymane Abdoul-Azize
Orai1 channel capacity to control store-operated Ca2+ entry (SOCE) and B-cell functions is poorly understood and more specifically in B-cell cancers, including human lymphoma and leukemia. As compared to normal B-cells, Orai1 is overexpressed in B-chronic lymphocytic leukemia (B-CLL) and contributes in resting B-CLL to mediate an elevated basal Ca2+ level through a constitutive Ca2+ entry, and in BCR-activated B-cell to regulate the Ca2+ signaling response. Such observations were confirmed in human B-cell lymphoma and leukemia lines, including RAMOS, JOK-1, MEC-1 and JVM-3 cells...
March 27, 2024: European Journal of Pharmacology
#30
JOURNAL ARTICLE
Chandrasekar Muthiah, Ravi Narra, Ehab Atallah, Wanlin Juan, Aniko Szabo, Guru Subramanian Guru Murthy
In the last decade, novel agents such as BTK and BCL-2 inhibitors have revolutionized treatment of CLL/SLL, with clinical trials showing improved overall survival compared to chemotherapeutic agents. However, studies examining whether they have improved overall survival at the population level are lacking. We evaluated this by conducting a retrospective analysis of CLL/SLL patients registered in the National Cancer Institute's surveillance epidemiology and end results (SEER) database, analyzing overall survival (OS) in periods pre- and post-availability of novel agents, along with demographic information...
March 22, 2024: Leukemia Research
#31
Trung Minh Nguyen, Eva Amenta, Lynne Chapman, Sarvari Yellapragada, Bhuvaneswari Krishnan, Jonathan Lim, Richard J Hamill
The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib...
2024: Therapeutic Advances in Infectious Disease
#32
JOURNAL ARTICLE
Aisha Hameed, Nadia Sajid, Muhammad Fayyaz, Shagufta Khaliq
OBJECTIVES: To determine validity of the CLL International prognostic index (IPI) scoring system in Pakistani chronic lymphocytic leukemia patients, as the validity and universal applicability of various prognostic scoring systems such as the CLL-IPI remains a challenge, particularly in under-developed countries like Pakistan. METHODS: This prospective single center study was conducted at Department of Hematology, University of Health Sciences, Lahore and included sixty patients with CLL diagnosed between July, 2019 to July, 2022...
2024: Pakistan Journal of Medical Sciences Quarterly
#33
JOURNAL ARTICLE
Francesca Romana Liberati, Sara Di Russo, Lorenzo Barolo, Giovanna Peruzzi, Maria Vittoria Farina, Sharon Spizzichino, Federica Di Fonzo, Deborah Quaglio, Luca Pisano, Bruno Botta, Alessandra Giorgi, Alberto Boffi, Francesca Cutruzzolà, Alessio Paone, Paola Baiocco
Chronic lymphocytic leukemia (CLL) is a widespread type of leukemia that predominantly targets B lymphocytes, undermining the balance between cell proliferation and apoptosis. In healthy B cells, miR-15/16, a tandem of microRNAs, functions as a tumor suppressor, curbing the expression of the antiapoptotic B cell lymphoma 2 protein (Bcl-2). Conversely, in CLL patients, a recurring deletion on chromosome 13q14, home to the miR15-a and miR16-1 genes, results in Bcl-2 overexpression, thereby fostering the onset of the pathology...
March 14, 2024: Pharmaceutics
#34
REVIEW
Samir Mouhssine, Nawar Maher, Bassam Francis Matti, Alaa Fadhil Alwan, Gianluca Gaidano
The B cell receptor (BCR) signaling pathway plays a crucial role in B cell development and contributes to the pathogenesis of B cell neoplasms. In B cell malignancies, the BCR is constitutively active through both ligand-dependent and ligand-independent mechanisms, resulting in continuous Bruton tyrosine kinase (BTK) signaling activation, which provides a survival and proliferation advantage to the neoplastic clone. Among B cell malignancies, those in which the most significant results were obtained by treatment with BTK inhibitors (BTKi) include chronic lymphocytic leukemia, mantle cell lymphoma, lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma...
March 12, 2024: International Journal of Molecular Sciences
#35
JOURNAL ARTICLE
Danijela Lekovic, Jelena Ivanovic, Tatjana Terzic, Maja Perunicic Jovanovic, Marija Dencic Fekete, Jelica Jovanovic, Isidora Arsenovic, Vojin Vukovic, Jelena Bila, Andrija Bogdanovic, Darko Antic
Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22-69)...
March 21, 2024: Journal of Clinical Medicine
#36
REVIEW
Aasem Abu Shtaya, Inbal Kedar, Lily Bazak, Lina Basel-Salmon, Sarit Farage Barhom, Michal Naftali, Marina Eskin-Schwartz, Ohad S Birk, Shirley Polager-Modan, Nitzan Keidar, Gili Reznick Levi, Zohar Levi, Tamar Yablonski-Peretz, Ahmad Mahamid, Ori Segol, Reut Matar, Yifat Bareli, Noy Azoulay, Yael Goldberg
POT1 (Protection of Telomeres 1) is a key component of the six-membered shelterin complex that plays a critical role in telomere protection and length regulation. Germline variants in the POT1 gene have been implicated in predisposition to cancer, primarily to melanoma and chronic lymphocytic leukemia (CLL). We report the identification of POT1 p.(I78T), previously ranked with conflicting interpretations of pathogenicity, as a founder pathogenic variant among Ashkenazi Jews (AJs) and describe its unique clinical landscape...
March 13, 2024: Genes
#37
JOURNAL ARTICLE
Reginald Gorczynski
The field of clinical oncology has been revolutionized over the past decade with the introduction of many new immunotherapies the existence of which have depended to a large extent on experimentation with both in vitro analysis and the use of various animal models, including gene-modified mice. The discussion below will review my own laboratory's studies, along with those of others in the field, on cancer immunotherapy. Our own studies have predominantly dwelt on two models of malignancy, namely a solid tumor model (breast cancer) and lymphoma...
February 25, 2024: Genes
#38
JOURNAL ARTICLE
Josipa Skelin, Maja Matulić, Lidija Milković, Darko Heckel, Jelena Skoko, Kristina Ana Škreb, Biljana Jelić Puškarić, Ika Kardum-Skelin, Lipa Čičin-Šain, Delfa Radić-Krišto, Mariastefania Antica
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by a specific expansion of mature B-cell clones. We hypothesized that the disease has a heterogeneous clinical outcome that depends on the genes and signaling pathways active in the malignant clone of the individual patient. It was found that several signaling pathways are active in CLL, namely, NOTCH1, the Ikaros family genes, BCL2, and NF-κB, all of which contribute to cell survival and the proliferation of the leukemic clone...
February 26, 2024: Biomedicines
#39
JOURNAL ARTICLE
Francesca Romana Mauro, Potito Rosario Scalzulli, Lydia Scarfò, Carla Minoia, Roberta Murru, Paolo Sportoletti, Ferdinando Frigeri, Francesco Albano, Nicola Di Renzo, Alessandro Sanna, Luca Laurenti, Massimo Massaia, Ramona Cassin, Marta Coscia, Caterina Patti, Elsa Pennese, Agostino Tafuri, Annalisa Chiarenza, Piero Galieni, Omar Perbellini, Carmine Selleri, Catello Califano, Felicetto Ferrara, Antonio Cuneo, Marco Murineddu, Gaetano Palumbo, Ilaria Scortechini, Alessandra Tedeschi, Livio Trentin, Marzia Varettoni, Fabrizio Pane, Anna Marina Liberati, Francesco Merli, Lucia Morello, Gerardo Musuraca, Monica Tani, Adalberto Ibatici, Giulia Regazzoni, Michele Di Candia, Maria Palma, Danilo Arienti, Stefano Molica
Real-world data in clinical practice are needed to confirm the efficacy and safety that ibrutinib has demonstrated in clinical trials of patients with chronic lymphocytic leukemia (CLL). We described the real-world persistence rate, patterns of use, and clinical outcomes in 309 patients with CLL receiving single-agent ibrutinib in first line (1L, n = 118), 2L ( n = 127) and ≥3L ( n = 64) in the prospective, real-world, Italian EVIdeNCE study. After a median follow-up of 23.9 months, 29.8% of patients discontinued ibrutinib (1L: 24...
March 20, 2024: Cancers
#40
JOURNAL ARTICLE
Francesco Angotzi, Alessandro Cellini, Valeria Ruocco, Chiara Adele Cavarretta, Ivan Zatta, Andrea Serafin, Stefano Pravato, Elisa Pagnin, Laura Bonaldi, Federica Frezzato, Monica Facco, Francesco Piazza, Livio Trentin, Andrea Visentin
Chronic lymphocytic leukemia (CLL) exhibits substantial variability in disease course. The mutational status of the B-cell receptor immunoglobulin heavy variable (IGHV) chain is a critical prognostic factor, categorizing patients into mutated (M-IGHV) and unmutated (U-IGHV) groups. Recently, a third subgroup with borderline mutational status (BL-IGHV) has been identified, comprising approximately 5% of CLL cases. This study retrospectively analyzes the outcomes of 30 BL-IGHV mutated patients among a cohort of 653 CLL patients, focusing on time to first treatment (TTFT) and overall survival (OS)...
March 8, 2024: Cancers
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