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https://www.readbyqxmd.com/read/28922373/dynein-light-chain-regulates-adaptive-and-innate-b-cell-development-by-distinctive-genetic-mechanisms
#1
Ashleigh King, Lingli Li, David M Wong, Rui Liu, Rebecca Bamford, Andreas Strasser, David M Tarlinton, Jörg Heierhorst
Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, "natural" antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development...
September 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28893938/epstein-barr-virus-associated-lymphomas
#2
REVIEW
Claire Shannon-Lowe, Alan B Rickinson, Andrew I Bell
Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis...
October 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28892044/a-novel-mouse-model-of-rhabdomyosarcoma-underscores-the-dichotomy-of-mdm2-alt1-function-in-vivo
#3
D F Comiskey, A G Jacob, B L Sanford, M Montes, A K Goodwin, H Steiner, E Matsa, A S Tapia-Santos, T W Bebee, J Grieves, K La Perle, P Boyaka, D S Chandler
Alternative splicing of the oncogene murine double minute 2 (MDM2) is induced in response to genotoxic stress. MDM2-ALT1, the major splice variant generated, is known to activate the p53 pathway and impede full-length MDM2's negative regulation of p53. Despite this perceptible tumor-suppressive role, MDM2-ALT1 is also associated with several cancers. Furthermore, expression of MDM2-ALT1 has been observed in aggressive metastatic disease in pediatric rhabdomyosarcoma (RMS), irrespective of histological subtype...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28885612/understanding-cd30-biology-and-therapeutic-targeting-a-historical-perspective-providing-insight-into-future-directions
#4
REVIEW
C A van der Weyden, S A Pileri, A L Feldman, J Whisstock, H M Prince
CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target...
September 8, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28882984/transient-apoptosis-inhibition-in-donor-stem-cells-improves-hematopoietic-stem-cell-transplantation
#5
Matthias Kollek, Gesina Voigt, Christian Molnar, Fabronia Murad, Daniela Bertele, Christopher Felix Krombholz, Sheila Bohler, Verena Labi, Stefan Schiller, Mirjam Kunze, Stephan Geley, Charlotte M Niemeyer, Ana Garcia-Saez, Miriam Erlacher
During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity...
September 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28881594/the-mir-106a-363-xpcl1-mirna-cluster-induces-murine-t-cell-lymphoma-despite-transcriptional-activation-of-the-p27-kip1-cell-cycle-inhibitor
#6
Daniel A Kuppers, Thomas M Schmitt, Harry C Hwang, Lavanya Samraj, Bruce E Clurman, Matthew L Fero
The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities in vitro that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions in vivo. Mature miR-106a~363 (Mirc2) miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or Kis2), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875507/the-etiology-of-b-cell-lymphoid-malignancies-with-a-focus-on-chronic-inflammation-and-infections
#7
Karin E Smedby, Maurilio Ponzoni
B-cell malignancies are a heterogeneous group of lymphoproliferative disorders with different molecular characteristics and clinical course. It is increasingly recognized that the group displays considerable heterogeneity also regarding etiologic factors. Here, we summarize the latest developments in the etiology of B-cell lymphoid malignancy subtypes focusing on immune perturbation. Severe immune suppression constitues a strong and well established risk factor for aggressive subtypes (e.g., diffuse large B-cell and Burkitt lymphoma), but appears unrelated to risk of common low-grade subtypes (e...
September 5, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28855351/non-hodgkin-and-hodgkin-lymphomas-select-for-overexpression-of-bclw
#8
Clare M Adams, Ramkrishna Mitra, Jerald Gong, Christine M Eischen
PURPOSE: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an anti-apoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other anti-apoptotic BCL2 family members in six different B-cell lymphomas...
August 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28835489/epstein-barr-virus-lmp1-mediated-oncogenicity
#9
Liang Wei Wang, Sizun Jiang, Benjamin E Gewurz
Epstein-Barr virus Latent Membrane Protein 1 (LMP1) is expressed in multiple human malignancies, including nasopharynegeal carcinoma, Hodgkin and immunosuppression-associated lymphomas. LMP1 mimics CD40 signaling to activate multiple growth and survival pathways, in particular NF-κB. LMP1 has critical roles in EBV-driven B-cell transformation, and its expression causes fatal lymphoproliferative disease in immunosuppressed mice. Here, we review recent developments in studies of LMP1 signaling, LMP1-induced host dependency factors, mouse models of LMP1 lymphomagenesis and anti-LMP1 immunotherapy approaches...
August 23, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28831000/inactivation-of-crebbp-expands-the-germinal-center-b-cell-compartment-down-regulates-mhcii-expression-and-promotes-dlbcl-growth
#10
Hind Hashwah, Corina A Schmid, Sabrina Kasser, Katrin Bertram, Anna Stelling, Markus G Manz, Anne Müller
The genes encoding the histone acetyl-transferases (HATs) CREB binding protein (CREBBP) and EP300 are recurrently mutated in the activated B cell-like and germinal center (GC) B cell-like subtypes of diffuse large B cell lymphoma (DLBCL). Here, we introduced a patient mutation into a human DLBCL cell line using CRISPR and deleted Crebbp and Ep300 in the GC B cell compartment of mice. CREBBP-mutant DLBCL clones exhibited reduced histone H3 acetylation, expressed significantly less MHCII, and grew faster than wild-type clones in s...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28825697/early-loss-of-crebbp-confers-malignant-stem-cell-properties-on-lymphoid-progenitors
#11
Sarah J Horton, George Giotopoulos, Haiyang Yun, Shabana Vohra, Olivia Sheppard, Rachael Bashford-Rogers, Mamunur Rashid, Alexandra Clipson, Wai-In Chan, Daniel Sasca, Loukia Yiangou, Hikari Osaki, Faisal Basheer, Paolo Gallipoli, Natalie Burrows, Ayşegül Erdem, Anastasiya Sybirna, Sarah Foerster, Wanfeng Zhao, Tonci Sustic, Anna Petrunkina Harrison, Elisa Laurenti, Jessica Okosun, Daniel Hodson, Penny Wright, Ken G Smith, Patrick Maxwell, Jude Fitzgibbon, Ming Q Du, David J Adams, Brian J P Huntly
Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis...
September 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28807016/endogenous-controls-of-gene-expression-in-n-methyl-n-nitrosourea-induced-t-cell-lymphoma-in-p53-deficient-mice
#12
Xi Wu, Susu Liu, Jianjun Lyu, Shuya Zhou, Yanwei Yang, Chenfei Wang, Wenda Gu, Qin Zuo, Baowen Li, Changfa Fan
BACKGROUND: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28800127/mnt-modulates-myc-driven-lymphomagenesis
#13
Kirsteen J Campbell, Cassandra J Vandenberg, Natasha S Anstee, Peter J Hurlin, Suzanne Cory
The transcriptional represser Mnt is a functional antagonist of the proto-oncoprotein Myc. Both Mnt and Myc utilise Max as an obligate partner for DNA binding, and Myc/Max and Mnt/Max complexes compete for occupancy at E-box DNA sequences in promoter regions. We have previously shown in transgenic mouse models that the phenotype and kinetics of onset of haemopoietic tumours varies with the level of Myc expression. We reasoned that a decrease in the level of Mnt would increase the functional level of Myc and accelerate Myc-driven tumorigenesis...
August 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28767666/mismatch-repair-deficient-hematopoietic-stem-cells-are-preleukemic-stem-cells
#14
Yulan Qing, Stanton L Gerson
Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM), but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus...
2017: PloS One
https://www.readbyqxmd.com/read/28757417/mirnas-in-b-cell-lymphoma-molecular-mechanisms-and-biomarker-potential
#15
REVIEW
Carla Solé, Erika Larrea, Giovanni Di Pinto, Maitena Tellaetxe, Charles Henderson Lawrie
MicroRNAs (miRNAs) are small non-coding RNAs that regulate many human genes including those involved in normal B-cell development. When these miRNAs are aberrantly expressed in B-cells they play key pathogenetic roles in the development and maintenance of B-cell lymphomas and by association may serve as useful biomarkers. In this review, we provide an overview of the importance of miRNAs to B-cell lymphomagenesis, as well as considering their use as biomarkers, and their potential usefulness for the clinic.
October 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28747658/a-single-amino-acid-substitution-confers-b-cell-clonogenic-activity-to-the-hiv-1-matrix-protein-p17
#16
Cinzia Giagulli, Pasqualina D'Ursi, Wangxiao He, Simone Zorzan, Francesca Caccuri, Kristen Varney, Alessandro Orro, Stefania Marsico, Benoît Otjacques, Carlo Laudanna, Luciano Milanesi, Riccardo Dolcetti, Simona Fiorentini, Wuyuan Lu, Arnaldo Caruso
Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28734136/the-good-and-bad-of-targeting-cancer-associated-extracellular-matrix
#17
REVIEW
Sabina Sangaletti, Claudia Chiodoni, Claudio Tripodo, Mario P Colombo
The maintenance of tissue homeostasis requires extracellular matrix (ECM) remodeling. Immune cells actively participate in regenerating damaged tissues contributing to ECM deposition and shaping. Dysregulated ECM deposition characterizes fibrotic diseases and cancer stromatogenesis, where a chronic inflammatory state sustains the ECM increase. In cancer, the ECM fosters several steps of tumor progression, providing pro-survival and proliferative signals, promoting tumor cell dissemination via collagen fibers or acting as a barrier to impede drug diffusion...
July 19, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28733424/camkii%C3%AE-stabilizes-myc-to-promote-t-cell-lymphomagenesis
#18
(no author information available yet)
Inhibition of CAMKIIγ reduces MYC protein levels, T-cell lymphomagenesis, and tumor burden in vivo.
July 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28727987/associations-of-autoimmunity-immunodeficiency-lymphomagenesis-and-gut-microbiota-in-mice-with-knockins-for-a-pathogenic-autoantibody
#19
Shweta Jain, Jerrold M Ward, Dong-Mi Shin, Hongsheng Wang, Zohreh Naghashfar, Alexander L Kovalchuk, Herbert C Morse
A number of mouse strains transgenic for B-cell receptors specific for nucleic acids or other autoantigens have been generated to understand how autoreactive B cells are regulated in normal and autoimmune mice. Previous studies of nonautoimmune C57BL/6 mice heterozygous for both the IgH and IgL knockins of the polyreactive autoantibody, 564, produced high levels of autoantibodies in a largely Toll-like receptor 7-dependent manner. Herein, we describe studies of mice homozygous for the knockins that also expressed high levels of autoantibodies but, unlike the heterozygotes, exhibited a high incidence of mature B-cell lymphomas and enhanced susceptibility to bacterial infections...
September 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28725161/ep300-single-nucleotide-polymorphism-rs20551-correlates-with-prolonged-overall-survival-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#20
Jiao Li, Ning Ding, Xiaogan Wang, Lan Mi, Lingyan Ping, Xuan Jin, Yalu Liu, Zhitao Ying, Yan Xie, Weiping Liu, Yuqin Song, Jun Zhu
BACKGROUND: Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown...
2017: Cancer Cell International
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