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REVIEW
Khalil Saleh, Morgane Cheminant, David Chiron, Barbara Burroni, Vincent Ribrag, Clémentine Sarkozy
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab-anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and are ideal candidates for novel targeted therapies (such as BTK, proteasome or BCL2 inhibitors, Immunomodulatory Drugs (IMiDs), bispecific antibodies, or CAR-T cell therapy)...
June 30, 2022: Cancers
#22
Guangming Zhang, Yongfeng Wang, Xiaoyong Han, Tingting Lu, Liangyin Fu, Haojie Jin, Kehu Yang, Hui Cai
Background: Cancer is one of the leading causes of death worldwide. Early diagnosis can significantly lower cancer-related mortality. Studies have shown that the lncRNA Forkhead box P4 antisense RNA 1 (FOXP4-AS1) is aberrantly expressed in various solid tumors. A meta-analysis was performed to evaluate the correlation of FOXP4-AS1 with the prognosis of cancer patients and determine the clinical value of FOXP4-AS1 as a potential diagnostic marker. Methods: Correlational studies from the Web of Science, Embase, OVID, Cochrane and PubMed databases were screened (up to April 1, 2021)...
2022: Frontiers in Oncology
#23
REVIEW
Thomas E Lew, John F Seymour
BH3-mimetics are a novel drug class of small molecule inhibitors of BCL2 family proteins which restore apoptosis in malignant cells. The only currently approved BH3-mimetic, the selective BCL2 inhibitor venetoclax, is highly efficacious in chronic lymphocytic leukemia and has rapidly advanced to an approved standard of care in frontline and relapsed disease in combination with anti-CD20 monoclonal antibodies. In this context, tumour lysis syndrome and myelosuppression are the most commonly encountered toxicities and are readily manageable with established protocols...
June 3, 2022: Journal of Hematology & Oncology
#24
JOURNAL ARTICLE
Giovanna Roncador, Joan Puñet-Ortiz, Lorena Maestre, Luis Gerardo Rodríguez-Lobato, Scherezade Jiménez, Ana Isabel Reyes-García, Álvaro García-González, Juan F García, Miguel Ángel Piris, Santiago Montes-Moreno, Manuel Rodríguez-Justo, Mari-Pau Mena, Carlos Fernández de Larrea, Pablo Engel
CD229 (Ly9) homophilic receptor, which belongs to the SLAM family of cell-surface molecules, is predominantly expressed on B and T cells. It acts as a signaling molecule, regulating lymphocyte homoeostasis and activation. Studies of CD229 function indicate that this receptor functions as a regulator of the development of marginal-zone B cells and other innate-like T and B lymphocytes. The expression on leukemias and lymphomas remains poorly understood due to the lack of CD229 monoclonal antibodies (mAb) for immunohistochemistry application (IHC)...
April 26, 2022: Cancers
#25
JOURNAL ARTICLE
Anita Kumar, Toby A Eyre, Katharine L Lewis, Meghan C Thompson, Chan Y Cheah
Mantle cell lymphoma is a rare B-cell non-Hodgkin lymphoma that is clinically and biologically heterogeneous. Risk stratification at the time of diagnosis is critical. One of the most powerful prognostic indices is the Mantle Cell Lymphoma International Prognostic Index-Combined, which integrates an estimate of proliferation (Ki67 index) with the standard Mantle Cell Lymphoma International Prognostic Index clinical factors. In addition, the presence of TP53 mutation is associated with suboptimal response to intensive chemoimmunotherapy and particularly dismal survival outcomes...
April 2022: American Society of Clinical Oncology Educational Book
#26
REVIEW
Junhun Cho
Immunohistochemistry is a technique that uses antigen-antibody interactions to detect specific proteins in cells. This technique has several essential applications in lymphoma diagnosis, including identifying the cell lineage and phase of maturation, detecting specific genetic alterations, visualizing the degree of cell proliferation, and identifying therapeutic targets. CD3 is a pan T-cell marker expressed on most of the mature T/NK-cell lymphomas, except for anaplastic large cell lymphoma, whereas CD20 is a pan B-cell marker that is expressed on most of the mature B-cell lymphomas...
April 30, 2022: Blood Research
#27
REVIEW
Etienne Leveille, Lai N Chan, Abu-Sayeef Mirza, Kohei Kume, Markus Müschen
SYK and ZAP70 nonreceptor tyrosine kinases serve essential roles in initiating B-cell receptor (BCR) and T-cell receptor (TCR) signaling in B- and T-lymphocytes, respectively. Despite their structural and functional similarity, expression of SYK and ZAP70 is strictly separated during B- and T-lymphocyte development, the reason for which was not known. Aberrant co-expression of ZAP70 with SYK was first identified in B-cell chronic lymphocytic leukemia (CLL) and is considered a biomarker of aggressive disease and poor clinical outcomes...
June 2022: Cellular Signalling
#28
REVIEW
Jing Zhang, Xueying Lu, Jianyong Li, Yi Miao
The advent of BTK inhibitors has changed the treatment of patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The first-in-class BTK inhibitor ibrutinib has shown remarkable therapeutic effects and manageable toxicities in multiple clinical trials. The second-generation BTK inhibitors, including acalabrutinib and zanubrutinib, also show remarkable efficacies. However, using BTK inhibitors as monotherapies requires continuous treatment. Resistance to BTK inhibitors and severe side effects unavoidably occur during BTK inhibitor monotherapy, frequently resulting in treatment failure...
April 4, 2022: Biomarker Research
#29
JOURNAL ARTICLE
Yeong Hak Bang, Joon Ho Shim, Kyung Ju Ryu, Yeon Jeong Kim, Myung Eun Choi, Sang Eun Yoon, Junhun Cho, Bon Park, Woong-Yang Park, Won Seog Kim, Seok Jin Kim
Background: The clinical utility of mRNA cargo in exosomes is unclear, although exosomes have potential as non-invasive biomarkers. This study aimed to investigate the feasibility of exosomal mRNA sequencing for monitoring disease status and predicting outcomes in non-Hodgkin lymphoma (NHL) patients. Methods: Exosomes were isolated from archived serum samples of 33 patients with NHL who were registered into our prospective cohort: diffuse large B-cell lymphoma (DLBCL, n = 17), intravascular B-cell lymphoma (IVL, n = 1), primary mediastinal large B-cell lymphoma (PMBL, n = 4), follicular lymphoma (FL, n = 3), mantle cell lymphoma (MCL, n = 3), and extranodal NK/T-cell lymphoma (ENKTL, n = 5)...
2022: Journal of Cancer
#30
RANDOMIZED CONTROLLED TRIAL
Rahul Lakhotia, Christopher Melani, Kieron Dunleavy, Stefania Pittaluga, Nakhle Saba, Liza Lindenberg, Esther Mena, Ethan Bergvall, Andrea Nicole Lucas, Allison Jacob, Erik Yusko, Seth M Steinberg, Elaine S Jaffe, Adrian Wiestner, Wyndham H Wilson, Mark Roschewski
Mantle cell lymphoma (MCL) is biologically and clinically heterogeneous and would benefit from prognostic biomarkers to guide management. Circulating tumor DNA (ctDNA) is a novel prognostic biomarker in diffuse large B-cell lymphoma that may have applicability in MCL. We analyzed ctDNA dynamics in previously untreated patients with MCL who received induction therapy with bortezomib and DA-EPOCH-R for 6 cycles followed by random assignment to observation or bortezomib maintenance in responding patients in a prospective phase 2 study...
April 26, 2022: Blood Advances
#31
JOURNAL ARTICLE
Panayiotis Panayiotidis, Gayane Tumyan, Catherine Thieblemont, Vadim V Ptushkin, Ana Marin-Niebla, Ramon García-Sanz, Steven Le Gouill, Anastasios Stathis, Alessia Bottos, Habib Hamidi, Pablo Katz, Thomas Perretti, Jenna C Willis, Christian Buske
We report efficacy, safety and biomarker data from a phase-II study evaluating atezolizumab (eight 21-day cycle as induction therapy) in combination with obinutuzumab in patients with relapsed/refractory mantle cell lymphoma (MCL, n = 30) or Waldenström's macroglobulinemia (WM, n = 4), and in combination with rituximab in patients with marginal zone lymphoma (MZL, n = 21). All patients received atezolizumab monotherapy as maintenance for ≤10 cycles. Objective response rates at end of induction were 16...
May 2022: Leukemia & Lymphoma
#32
JOURNAL ARTICLE
Esther K Elliott, Lloyd N Hopkins, Robert Hensen, Heidi G Sutherland, Larisa M Haupt, Lyn R Griffiths
MicroRNAs (miRNAs) are well known for their ability to regulate the expression of specific target genes through degradation or inhibition of translation of the target mRNA. In various cancers, miRNAs regulate gene expression by altering the epigenetic status of candidate genes that are implicated in various difficult to treat haematological malignancies such as non-Hodgkin lymphoma by acting as either oncogenes or tumour suppressor genes. Cellular and circulating miRNA biomarkers could also be directly utilised as disease markers for diagnosis and monitoring of non-Hodgkin lymphoma (NHL); however, the role of DNA methylation in miRNA expression regulation in NHL requires further scientific inquiry...
2021: Frontiers in Genetics
#33
JOURNAL ARTICLE
Katrine Melvold, Mariaserena Giliberto, Linda Karlsen, Pilar Ayuda-Durán, Robert Hanes, Toril Holien, Jorrit Enserink, Jennifer R Brown, Geir E Tjønnfjord, Kjetil Taskén, Sigrid S Skånland
Most patients with chronic lymphocytic leukemia (CLL) initially respond to targeted therapies, but eventually relapse and develop resistance. Novel treatment strategies are therefore needed to improve patient outcomes. Here, we performed direct drug testing on primary CLL cells and identified synergy between eight different mitogen-activated protein kinase kinase (MEK) inhibitors and the B-cell lymphoma 2 (Bcl-2) antagonist venetoclax. Drug sensitivity was independent of immunoglobulin heavy-chain gene variable region (IGVH) and tumor protein p53 (TP53) mutational status, and CLL cells from idelalisib-resistant patients remained sensitive to the treatment...
March 2022: Molecular Oncology
#34
MULTICENTER STUDY
Jacob D Soumerai, Anthony R Mato, Ahmet Dogan, Venkatraman E Seshan, Erel Joffe, Kelsey Flaherty, Jason Carter, Ephraim Hochberg, Jeffrey A Barnes, Audrey M Hamilton, Jeremy S Abramson, Connie L Batlevi, Matthew J Matasar, Ariela Noy, Colette N Owens, M Lia Palomba, Anita Kumar, Tak Takvorian, Ai Ni, Morgan Choma, Chaya Friedman, Puja Chadha, Elizabeth Simkins, Jade Ruiters, Sidney Sechio, Daneal Portman, Lauren Ramos, Natascha Nolet, Neena Mahajan, Rosalba Martignetti, Joanna Mi, Krista Scorsune, Julia Lynch, Brianne McGree, Stephanie Hughes, Clare Grieve, Lindsey E Roeker, Meghan Thompson, P Connor Johnson, Mikhail Roshal, Jane Huang, Juliana Biondo, Qun Wu, Allison Jacob, Omar Abdel-Wahab, Andrew D Zelenetz
BACKGROUND: We hypothesised that combining zanubrutinib with obinutuzumab and venetoclax (BOVen) as an initial therapy for chronic lymphocytic leukaemia and small lymphocytic lymphoma would lead to high rates of undetectable minimal residual disease (MRD), and we explored MRD as a biomarker for directing treatment duration. METHODS: This multicenter, investigator-initiated, single-arm, phase 2 trial took place at two two academic medical centres in the USA. Patients were eligible for the primary cohort if they had treatment-naive chronic lymphocytic leukaemia or small lymphocytic lymphoma, required therapy, and were at least 18 years of age with an Eastern Cooperative Oncology Group performance status up to 2...
December 2021: Lancet Haematology
#35
JOURNAL ARTICLE
Xiaobin Wang, Fazal Shirazi, Wei Yan, Xiaoyu Liu, Hua Wang, Robert Z Orlowski, Huihan Wang
Mantle cell lymphoma (MCL) is a haematologic malignancy. The proteasome inhibitor (PI) bortezomib has been approved to treat MCL, but resistance has emerged through mechanisms that remain unclear. This study aimed to explore the mechanism of PI resistance in MCL and identify new targets for this patient subgroup. Carfilzomib-resistant (CR) MCL cell lines and primary samples were used for both in vitro and in vivo experiments to identify gene expression and explore their related signalling pathways. We first identified mucin 20 (MUC20) suppression in carfilzomib-resistant MCL models...
November 2021: Journal of Cellular and Molecular Medicine
#36
Arati A Inamdar, Abraham Loo, Nagy Mikhail, Patrick Lee
Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma (NHL) with a dismal prognosis. The pathogenesis of MCL is complex and involves molecular alterations in various genes and pathways including the regulatory elements of the cell cycle machinery and senescence, DNA damage response pathways, and cell survival signals. Currently, Mantle Cell Lymphoma International Prognostic Index (MIPI) score and proliferative gene markers. TP53 and CDKN2A alterations are being used for the prognosis of MCL patients...
August 2021: Curēus
#37
JOURNAL ARTICLE
Jun Wang, Hui Xu, Shuang Ge, Chaoshuai Xue, Hailing Li, Xiaotong Jing, Ke Liang, Xiaoying Zhang, Cuijuan Zhang
OBJECTIVE: The function of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) has been studied in several cancers; however, little is known about its role in mantle cell lymphoma (MCL). Thus, this study aimed to characterize the significance and function of EHMT2 in MCL. METHODS: EHMT2 expression in MCL and reactive hyperplasia (RH) were investigated by immunohistochemistry. Genome-wide analysis of DNA methylation was performed on EHMT2 + MCL samples. The function of EHMT2 was determined by CCK8, flow cytometry, and western blot assays...
October 12, 2021: Cancer Biology & Medicine
#38
JOURNAL ARTICLE
Daniel Xia, Alberto Jose Leon, Jiong Yan, Anjali Silva, Mehran Bakhtiari, Rosemarie Tremblay-LeMay, Shamini Selvarajah, Peter Sabatini, Phedias Diamandis, Trevor Pugh, Robert Kridel, Jan Delabie
Although most small B-cell lymphomas (SBCLs) can be diagnosed using routine methods, challenges exist. For example, marginal zone lymphomas (MZLs) can be difficult to rule-in, in large part because no widely-used, sensitive, and specific biomarker is available for the marginal zone cell of origin. In this study, it was hypothesized that DNA methylation array profiling can assist with the classification of SBCLs, including MZLs. Extramedullary SBCLs, including challenging cases, were reviewed internally for pathology consensus and profiled...
December 2021: Journal of Molecular Diagnostics: JMD
#39
REVIEW
Olga Kersy, Mali Salmon-Divon, Ofer Shpilberg, Oshrat Hershkovitz-Rokah
B-lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies are of B-cell origin, suggesting that the development and activation of B cells must be tightly regulated. In recent years, differentially expressed non-coding RNAs have been identified in mantle cell lymphoma (MCL) tumor samples as opposed to their naive, normal B-cell compartment. These aberrantly expressed molecules, specifically microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), have a role in cellular growth and survival pathways in various biological models...
August 31, 2021: International Journal of Molecular Sciences
#40
Fu-Chou Lee, Junn-Liang Chang, Hung-Ming Chen, Wan-Chen Tsai, Po-Jen Hsiao
BACKGROUND: Acute abdominal syndrome can be caused by several possible reasons. The most common causes are perforation of a gastroduodenal ulcer, peritonitis, intestinal obstructions, and perforation of an appendix or fallopian tube. Fever and pain can be caused by an appendicitis or sigmoiditis. Appendiceal lymphoma is a rare disease that is usually found incidentally during appendectomy. Most of the cases are non-Hodgkin's lymphomas. Mantle cell lymphoma is an aggressive B-cell non-Hodgkin's lymphoma with a poorer prognosis than other B-cell lymphomas; thus, a definitive diagnosis is essential...
August 5, 2021: Healthcare (Basel, Switzerland)
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