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https://www.readbyqxmd.com/read/29774105/pre-clinical-activity-of-targeting-the-pi3k-akt-mtor-pathway-in-burkitt-lymphoma
#1
Maria Bhatti, Thomas Ippolito, Cory Mavis, Juan Gu, Mitchell S Cairo, Megan S Lim, Francisco Hernandez-Ilizaliturri, Matthew J Barth
Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been implicated in Burkitt lymphomagenesis and increased PI3K/AKT activation has been associated with worse outcomes in adults with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Inhibitors of the PI3K/AKT pathway have been approved for the treatment of refractory indolent B-NHL and continue to be investigated for treatment of aggressive B-NHLs...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#2
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29756258/a-prospective-analysis-of-circulating-saturated-and-monounsaturated-fatty-acids-and-risk-of-non-hodgkin-lymphoma
#3
Yu-Han Chiu, Kimberly A Bertrand, Shumin Zhang, Francine Laden, Mara M Epstein, Bernard A Rosner, Stephanie Chiuve, Hannia Campos, Edward L Giovannucci, Jorge E Chavarro, Brenda M Birmann
Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS)...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29746265/microenvironment-signaling-driving-lymphomagenesis
#4
Léa Verdière, Frédéric Mourcin, Karin Tarte
PURPOSE OF REVIEW: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment...
May 8, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29733294/human-herpesvirus-encoded-kinase-induces-b-cell-lymphomas-in-vivo
#5
Penny M Anders, Nathan D Montgomery, Stephanie A Montgomery, Aadra P Bhatt, Dirk P Dittmer, Blossom Damania
Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is the etiological agent of the endothelial cell cancer Kaposi's sarcoma (KS) and 2 B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV ORF36, also known as viral protein kinase (vPK), is a viral serine/threonine kinase. We previously reported that KSHV vPK enhances cell proliferation and mimics cellular S6 kinase to phosphorylate ribosomal protein S6, a protein involved in protein synthesis...
May 7, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29719024/molecular-advances-in-cutaneous-t-cell-lymphoma
#6
Armando N Bastidas Torres, Safa Najidh, Cornelis P Tensen, Maarten H Vermeer
Cutaneous T-cell lymphoma (CTCL) is a group of malignancies derived from skin-homing T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common CTCL variants. In recent years, the genetic landscape of SS/MF has been characterized using genome-wide nextgeneration sequencing approaches. These studies have revealed that genes subjected to oncogenic mutations take part in cell cycle regulation, chromatin modification, Janus kinase (JAK)-signal transducer and activator of transcription protein (STAT) signaling, T-cell receptor (TCR)/ nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and microtubule associated protein kinase (MAPK) signaling, which suggests that deregulation of these cellular processes underlies lymphomagenesis...
March 2018: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/29707540/lymphoma-and-lymphomagenesis-in-primary-sj%C3%A3-gren-s-syndrome
#7
REVIEW
Alessia Alunno, Maria Comasia Leone, Roberto Giacomelli, Roberto Gerli, Francesco Carubbi
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease mainly affecting exocrine glands and leading to impaired secretory function. The clinical picture is dominated by signs and symptoms of mucosal dryness and the course of the disease is mild and indolent in the majority of cases. However, a subgroup of patients can also experience extraglandular manifestations that worsen the disease prognosis. pSS patients are consistently found to have a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autimmune disorders and to the general population...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29702521/dna-damage-pathways-and-b-cell-lymphomagenesis
#8
Gero Knittel, Tim Rehkämper, Pascal Nieper, Anna Schmitt, Ruth Flümann, H Christian Reinhardt
PURPOSE OF REVIEW: Recent lymphoma genome sequencing projects have shed light on the genomic landscape of indolent and aggressive lymphomas, as well as some of the molecular mechanisms underlying recurrent mutations and translocations in these entities. Here, we review these recent genomic discoveries, focusing on acquired DNA repair defects in lymphoma. In addition, we highlight recently identified actionable molecular vulnerabilities associated with recurrent mutations in chronic lymphocytic leukemia (CLL), which serves as a model entity...
April 26, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29693246/germline-mutations-in-protection-of-telomeres-1-in-two-families-with-hodgkin-lymphoma
#9
Mary L McMaster, Chongkui Sun, Maria T Landi, Sharon A Savage, Melissa Rotunno, Xiaohong R Yang, Kristine Jones, Aurélie Vogt, Amy Hutchinson, Bin Zhu, Mingyi Wang, Belynda Hicks, Anand Thirunavukarason, Douglas R Stewart, Stella Koutros, Alisa M Goldstein, Stephen J Chanock, Neil E Caporaso, Margaret A Tucker, Lynn R Goldin, Yie Liu
In a previous whole exome sequencing of patients from 41 families with Hodgkin lymphoma, we identified two families with distinct heterozygous rare coding variants in POT1 (D224N and Y36H), both in a highly conserved region of the gene. POT1 D224N mutant did not bind to a single-stranded telomere oligonucleotide in vitro suggesting the mutation perturbs POT1's ability to bind to the telomeric G-rich overhang. Human HT1080 cells expressing POT1 D224N and lymphoblastoid cells carrying Y36H both showed increased telomere length and fragility in comparison to wild type cells...
May 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29689246/il-13-is-produced-by-tumor-cells-in-breast-implant-associated-anaplastic-large-cell-lymphoma-implications-for-pathogenesis
#10
Marshall E Kadin, John Morgan, Haiying Xu, Alan L Epstein, David Sieber, Bradley A Hubbard, William P Adams, Carlos E Bacchi, Joao C S Goes, Mark W Clemens, L Jeffrey Medeiros, Roberto N Miranda
More than 500 women worldwide have developed a CD30+ T-cell lymphoma around breast implants, strongly suggesting a cause and effect relationship, and designated as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The mechanism of lymphomagenesis is unknown. Recently, a bacterial biofilm containing gram negative bacilli was discovered on the surface of breast implants associated with ALCL. We and others have described overexpression of the proto-oncogene JUNB and mutations of JAK1/2, TP53 and STAT3 in BIA-ALCL...
April 21, 2018: Human Pathology
https://www.readbyqxmd.com/read/29666292/human-immunodeficiency-virus-tat-protein-aids-v-region-somatic-hypermutation-in-human-b-cells
#11
Xiaohua Wang, Zhi Duan, Guojun Yu, Manxia Fan, Matthew D Scharff
Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29662618/ectopic-expression-of-transcription-factor-batf3-induces-b-cell-lymphomas-in-a-murine-b-cell-transplantation-model
#12
Christian Weiser, Mina V Petkova, Benjamin Rengstl, Claudia Döring, Dorothee von Laer, Sylvia Hartmann, Ralf Küppers, Martin-Leo Hansmann, Sebastian Newrzela
The mechanisms involved in malignant transformation of mature B and T lymphocytes are still poorly understood. In a previous study, we compared gene expression profiles of the tumor cells of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) to their normal cellular counterparts and found the basic leucine zipper protein ATF-like 3 (BATF3) to be significantly upregulated in the tumor cells of both entities. To assess the oncogenic potential of BATF3 in lymphomagenesis and to dissect the molecular interactions of BATF3 in lymphoma cells, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag1-deficient recipients...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661169/rna-seq-reveals-the-existence-of-a-cdkn1c-e2f1-tp53-axis-that-is-altered-in-human-t-cell-lymphoblastic-lymphomas
#13
Pilar López-Nieva, Pablo Fernández-Navarro, Concepción Vaquero-Lorenzo, María Villa-Morales, Osvaldo Graña-Castro, María Ángeles Cobos-Fernández, José Luis López-Lorenzo, Pilar Llamas, Laura González-Sanchez, Isabel Sastre, Marina Pollan, Marcos Malumbres, Javier Santos, José Fernández-Piqueras
BACKGROUND: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas...
April 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29649101/pathobiologic-roles-of-epstein-barr-virus-encoded-micrornas-in-human-lymphomas
#14
REVIEW
Mohsen Navari, Maryam Etebari, Mostafa Ibrahimi, Lorenzo Leoncini, Pier Paolo Piccaluga
Epstein-Barr virus (EBV) is a human γ-herpesvirus implicated in several human malignancies, including a wide range of lymphomas. Several molecules encoded by EBV in its latent state are believed to be related to EBV-induced lymphomagenesis, among which microRNAs-small RNAs with a posttranscriptional regulating role-are of great importance. The genome of EBV encodes 44 mature microRNAs belonging to two different classes, including BamHI-A rightward transcript ( BART ) and Bam HI fragment H rightward open reading frame 1 ( BHRF1 ), with different expression levels in different EBV latency types...
April 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29615404/the-tumor-suppressive-tgf-%C3%AE-smad1-s1pr2-signaling-axis-is-recurrently-inactivated-in-diffuse-large-b-cell-lymphoma
#15
Anna Stelling, Hind Hashwah, Katrin Bertram, Markus G Manz, Alexandar Tzankov, Anne Müller
The sphingosine-1-phosphate receptor S1PR2 and its downstream signaling pathway are commonly silenced in diffuse large B-cell lymphoma (DLBCL), either by mutational inactivation or through negative regulation by the oncogenic transcription factor FOXP1. In this study, we examined the upstream regulators of S1PR2 expression and have newly identified the transforming growth factor-β (TGF-β)/TGF-βR2/SMAD1 axis as critically involved in S1PR2 transcriptional activation. Phosphorylated SMAD1 directly binds to regulatory elements in the S1PR2 locus as assessed by chromatin immunoprecipitation, and the CRISPR-mediated genomic editing of S1PR2 , SMAD1 , or TGFBR2 in DLBCL cell lines renders cells unresponsive to TGF-β-induced apoptosis...
May 17, 2018: Blood
https://www.readbyqxmd.com/read/29606020/hepatitis-b-reactivation-in-the-treatment-of-non-hodgkin-lymphoma
#16
Matthew Kelling, Lubomir Sokol, Samir Dalia
Chronic active hepatitis B infection (HBV) has been implicated in lymphomagenesis of non-Hodgkin lymphoma (NHL). Treatment of cancer including NHL with chemotherapy or immunotherapy can lead to HBV reactivation in previously infected patients. Serological testing of HBV prior to initiation of this therapy is recommended by several national and international medical agencies and expert panels. Patients with positive hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (anti-HBc ab) need to start antiviral therapy with entecavir or tenofovir prior to initiation of chemotherapy or immunotherapy and continue this treatment for 6 to 12 months after completion of cancer therapy to avoid late HBV reactivation...
January 2018: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/29601503/the-immunomodulatory-capacity-of-an-epstein-barr-virus-abortive-lytic-cycle-potential-contribution-to-viral-tumorigenesis
#17
REVIEW
Abigail Morales-Sánchez, Ezequiel M Fuentes-Panana
Epstein-Barr virus (EBV) is characterized by a bipartite life cycle in which latent and lytic stages are alternated. Latency is compatible with long-lasting persistency within the infected host, while lytic expression, preferentially found in oropharyngeal epithelial tissue, is thought to favor host-to-host viral dissemination. The clinical importance of EBV relates to its association with cancer, which we think is mainly a consequence of the latency/persistency mechanisms. However, studies in murine models of tumorigenesis/lymphomagenesis indicate that the lytic cycle also contributes to cancer formation...
March 30, 2018: Cancers
https://www.readbyqxmd.com/read/29575510/pathological-features-of-intestinal-t-cell-lymphoma-in-shiba-dogs-in-japan
#18
I Matsumoto, K Uchida, K Nakashima, Y Goto-Koshino, J K Chambers, H Tsujimoto, H Nakayama
Intestinal T-cell lymphoma is being more frequently diagnosed in dogs owing to the wide availability of endoscopy and clonality analysis in veterinary medicine. However, no epidemiological study on intestinal T-cell lymphoma has been previously performed, and hence, information about dog breed, age and sex distributions of intestinal T-cell lymphoma has largely remained unclear. In this study, breed predisposition to canine intestinal T-cell lymphoma was determined by calculating odds ratios and 95% confidential intervals...
March 25, 2018: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/29568300/tailoring-immune-responses-toward-autoimmunity-transcriptional-regulators-that-drive-the-creation-and-collusion-of-autoreactive-lymphocytes
#19
REVIEW
Kim L Good-Jacobson, Joanna R Groom
T-dependent humoral immune responses to infection involve a collaboration between B and CD4 T cell activation, migration, and co-stimulation, thereby culminating in the formation of germinal centers (GCs) and eventual differentiation into memory cells and long-lived plasma cells (PCs). CD4 T cell-derived signals drive the formation of a tailored B cell response. Downstream of these signals are transcriptional regulators that are the critical enactors of immune cell programs. In particular, a core group of transcription factors regulate both B and T cell differentiation, identity, and function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29549872/targeting-the-b-cell-receptor-pathway-in-diffuse-large-b-cell-lymphoma
#20
REVIEW
Kieron Dunleavy, Tabea Erdmann, Georg Lenz
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category with different molecular subtypes defined by distinct gene expression patterns and divergent mechanisms of oncogenic activation. Several studies have suggested an inferior survival for patients of the activated B-cell-like (ABC) versus the germinal center B-cell-like (GCB) DLBCL subtype which has led to increasing interest in investigating pharmacological inhibition of signaling pathways which contribute to lymphomagenesis and that are specifically utilized by ABC DLBCL cells...
April 2018: Cancer Treatment Reviews
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