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Lossos Izidore

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https://www.readbyqxmd.com/read/29745744/rapid-complete-response-to-blinatumomab-as-a-successful-bridge-to-allogeneic-stem-cell-transplantation-in-a-case-of-refractory-richter-syndrome
#1
Juan Pablo Alderuccio, Nicholas Mackrides, Jennifer R Chapman, Francisco Vega, Izidore S Lossos
No abstract text is available yet for this article.
May 10, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29327093/mir-181-family-specific-behavior-in-different-cancers-a-meta-analysis-view
#2
Cecilia Pop-Bica, Sebastian Pintea, Roxana Cojocneanu-Petric, Giannino Del Sal, Silvano Piazza, Zhao-Hui Wu, Alvaro J Alencar, Izidore S Lossos, Ioana Berindan-Neagoe, George A Calin
The involvement of microRNAs in malignant transformation and cancer progression was previously grounded. The observations made by multiple published studies led to the conclusion that some of these small sequences could be eventually used as biomarkers for diagnosis/prognosis. This meta-analysis investigated whether microRNA-181 family members could predict the outcome of patients carrying different types of cancer. We searched the PubMed and Embase databases for studies evaluating the expression levels of miR-181a/b/c/d in patients with cancer, selecting the publications that assessed the relation between low and high levels of one of these four microRNAs and patients' outcome...
March 2018: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29296913/clinicopathologic-consensus-study-of-gray-zone-lymphoma-with-features-intermediate-between-dlbcl-and-classical-hl
#3
Monika Pilichowska, Stefania Pittaluga, Judith A Ferry, Jessica Hemminger, Hong Chang, Jennifer A Kanakry, Laurie H Sehn, Tatyana Feldman, Jeremy S Abramson, Athena Kritharis, Francisco J Hernandez-Ilizaliturri, Izidore S Lossos, Oliver W Press, Timothy S Fenske, Jonathan W Friedberg, Julie M Vose, Kristie A Blum, Deepa Jagadeesh, Bruce Woda, Gaurav K Gupta, Randy D Gascoyne, Elaine S Jaffe, Andrew M Evens
Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+ , 83%; PAX5+ , 100%; BCL6+ , 20%; MUM1+ , 100%; CD30+ , 92%; EBV+ , 4%)...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29140403/klhl6-is-preferentially-expressed-in-germinal-center-derived-b-cell-lymphomas
#4
Christian A Kunder, Giovanna Roncador, Ranjana H Advani, Gabriela Gualco, Carlos E Bacchi, Jean M Sabile, Izidore S Lossos, Kexin Nie, Robert John Tibshirani, Michael R Green, Ash A Alizadeh, Yasodha Natkunam
Objectives: KLHL6 is a recently described BTB-Kelch protein with selective expression in lymphoid tissues and is most strongly expressed in germinal center B cells. Methods: Using gene expression profiling as well as immunohistochemistry with an anti-KLHL6 monoclonal antibody, we have characterized the expression of this molecule in normal and neoplastic tissues. Protein expression was evaluated in 1,058 hematopoietic neoplasms. Results: Consistent with its discovery as a germinal center marker, KLHL6 was positive mainly in B-cell neoplasms of germinal center derivation, including 95% of follicular lymphomas (106/112)...
November 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29096668/observational-study-of-lenalidomide-in-patients-with-mantle-cell-lymphoma-who-relapsed-progressed-after-or-were-refractory-intolerant-to-ibrutinib-mcl-004
#5
Michael Wang, Stephen J Schuster, Tycel Phillips, Izidore S Lossos, Andre Goy, Simon Rule, Mehdi Hamadani, Nilanjan Ghosh, Craig B Reeder, Evelyn Barnett, Marie-Laure Casadebaig Bravo, Peter Martin
BACKGROUND: The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. METHODS: The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. RESULTS: Of 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment...
November 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28351190/hepatosplenic-t-cell-lymphoma-associated-with-membranoproliferative-glomerulonephritis
#6
Shuo-Chieh Wu, Jennifer R Chapman, Francisco Vega, Neil Abrahams, Izidore S Lossos, Juan Pablo Alderuccio
No abstract text is available yet for this article.
March 28, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28137826/anti-cd20-interleukin-21-fusokine-targets-malignant-b-cells-via-direct-apoptosis-and-nk-cell-dependent-cytotoxicity
#7
Shruti Bhatt, Salma Parvin, Yu Zhang, Hyun-Mi Cho, Kranthi Kunkalla, Francisco Vega, John M Timmerman, Seung-Uon Shin, Joseph D Rosenblatt, Izidore S Lossos
In spite of newly emerging therapies and the improved survival of patients with non-Hodgkin lymphoma (NHL), relapses or primary refractory disease are commonly observed and associated with dismal prognosis. Although discovery of the anti-CD20 antibody rituximab has markedly improved outcomes in B-cell NHL, rituximab resistance remains an important obstacle to successful treatment of these tumors. To improve the efficacy of CD20-targeted therapy, we fused interleukin 21 (IL-21), which induces direct lymphoma cytotoxicity and activates immune effector cells, to the anti-CD20 antibody (αCD20-IL-21 fusokine)...
April 20, 2017: Blood
https://www.readbyqxmd.com/read/28122867/the-genetic-basis-of-hepatosplenic-t-cell-lymphoma
#8
Matthew McKinney, Andrea B Moffitt, Philippe Gaulard, Marion Travert, Laurence De Leval, Alina Nicolae, Mark Raffeld, Elaine S Jaffe, Stefania Pittaluga, Liqiang Xi, Tayla Heavican, Javeed Iqbal, Karim Belhadj, Marie Helene Delfau-Larue, Virginie Fataccioli, Magdalena B Czader, Izidore S Lossos, Jennifer R Chapman-Fredricks, Kristy L Richards, Yuri Fedoriw, Sarah L Ondrejka, Eric D Hsi, Lawrence Low, Dennis Weisenburger, Wing C Chan, Neha Mehta-Shah, Steven Horwitz, Leon Bernal-Mizrachi, Christopher R Flowers, Anne W Beaven, Mayur Parihar, Lucile Baseggio, Marie Parrens, Anne Moreau, Pierre Sujobert, Monika Pilichowska, Andrew M Evens, Amy Chadburn, Rex K H Au-Yeung, Gopesh Srivastava, William W L Choi, John R Goodlad, Igor Aurer, Sandra Basic-Kinda, Randy D Gascoyne, Nicholas S Davis, Guojie Li, Jenny Zhang, Deepthi Rajagopalan, Anupama Reddy, Cassandra Love, Shawn Levy, Yuan Zhuang, Jyotishka Datta, David B Dunson, Sandeep S Davé
Hepatosplenic T-cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole-exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy-number alterations in the disease. Chromatin-modifying genes, including SETD2, INO80 , and ARID1B , were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%), for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS , and TP53 SETD2 was the most frequently silenced gene in HSTL...
April 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28062691/activating-mutations-and-translocations-in-the-guanine-exchange-factor-vav1-in-peripheral-t-cell-lymphomas
#9
Francesco Abate, Ana C da Silva-Almeida, Sakellarios Zairis, Javier Robles-Valero, Lucile Couronne, Hossein Khiabanian, S Aidan Quinn, Mi-Yeon Kim, Maria Antonella Laginestra, Christine Kim, Danilo Fiore, Govind Bhagat, Miguel Angel Piris, Elias Campo, Izidore S Lossos, Olivier A Bernard, Giorgio Inghirami, Stefano Pileri, Xosé R Bustelo, Raul Rabadan, Adolfo A Ferrando, Teresa Palomero
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27982024/epstein-barr-virus-positive-follicular-lymphoma
#10
Nicholas Mackrides, German Campuzano-Zuluaga, Yvan Maque-Acosta, Adrienne Moul, Nouf Hijazi, Francis Offiong Ikpatt, Ronald Levy, Ramiro E Verdun, Kranthi Kunkalla, Yasodha Natkunam, Izidore S Lossos, Francisco Vega, Jennifer Chapman
Epstein-Barr virus (EBV) -associated follicular lymphoma is only rarely reported. Herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of EBV-associated follicular lymphoma occurring in unselected cases. Out of 382 analyzed cases, 10 EBV-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3-4.0%). All EBV-positive follicular lymphomas showed EBV-encoded small RNA-positive lymphoma cells present in a follicular distribution. Of these, eight also had tissue available for testing of expression of latent membrane protein 1 (LMP1), out of which six (75%) were positive...
April 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27789481/long-term-course-of-patients-with-primary-ocular-adnexal-malt-lymphoma-a-large-single-institution-cohort-study
#11
Amrita Desai, Madhura G Joag, Lazaros Lekakis, Jennifer R Chapman, Francisco Vega, Robert Tibshirani, David Tse, Arnold Markoe, Izidore S Lossos
While primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common orbital tumor, there are large gaps in knowledge of its natural history. We conducted a retrospective analysis of the largest reported cohort, consisting of 182 patients with POAML, diagnosed or treated at our institution to analyze long-term outcome, response to treatment, and incidence and localization of relapse and transformation. The majority of patients (80%) presented with stage I disease. Overall, 84% of treated patients achieved a complete response after first-line therapy...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/27649904/marginal-zone-dural-lymphoma-the-memorial-sloan-kettering-cancer-center-and-university-of-miami-experiences
#12
Macarena I de la Fuente, Aya Haggiagi, Adrienne Moul, Robert J Young, Charif Sidani, Arnold Markoe, Francisco Vega, Lisa M DeAngelis, Izidore S Lossos
Dural lymphoma (DL) is a rare type of primary CNS lymphoma arising from the dura mater. The optimal treatment is uncertain. A retrospective review was performed on 26 DL patients. Seventeen patients underwent resection and nine had a biopsy. Twenty three patients could be assessed for a response to treatment after surgery. Thirteen received focal radiotherapy (RT), six whole brain RT (WBRT), three chemotherapy alone and one chemotherapy followed by WBRT. Twenty two achieved complete response (CR) and one a partial response (PR)...
April 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27405876/interleukin-21-its-potential-role-in-the-therapy-of-b-cell-lymphomas
#13
REVIEW
Shruti Bhatt, Kristopher A Sarosiek, Izidore S Lossos
Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy...
January 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27252116/characteristics-and-outcomes-of-lymphoblastic-lymphoma-the-university-of-miami-experience
#14
LETTER
Juan Pablo Alderuccio, Pooja Amarapurkar, Jennifer R Chapman, Francisco Vega, Izidore S Lossos
No abstract text is available yet for this article.
January 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27151888/pathophysiological-significance-and-therapeutic-targeting-of-germinal-center-kinase-in-diffuse-large-b-cell-lymphoma
#15
Julie Marie Matthews, Shruti Bhatt, Matthew P Patricelli, Tyzoon K Nomanbhoy, Xiaoyu Jiang, Yasodha Natkunam, Andrew J Gentles, Ezequiel Martinez, Daxing Zhu, Jennifer Rose Chapman, Elena Cortizas, Ragini Shyam, Shideh Chinichian, Ranjana Advani, Li Tan, Jianming Zhang, Hwan Geun Choi, Robert Tibshirani, Sara J Buhrlage, Dita Gratzinger, Ramiro Verdun, Nathanael S Gray, Izidore S Lossos
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated...
July 14, 2016: Blood
https://www.readbyqxmd.com/read/26989201/gna13-loss-in-germinal-center-b-cells-leads-to-impaired-apoptosis-and-promotes-lymphoma-in-vivo
#16
Jane A Healy, Adrienne Nugent, Rachel E Rempel, Andrea B Moffitt, Nicholas S Davis, Xiaoyu Jiang, Jennifer R Shingleton, Jenny Zhang, Cassandra Love, Jyotishka Datta, Matthew E McKinney, Tiffany J Tzeng, Nina Wettschureck, Stefan Offermanns, Katelyn A Walzer, Jen-Tsan Chi, Suhail A K Rasheed, Patrick J Casey, Izidore S Lossos, Sandeep S Dave
GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre(+) GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro...
June 2, 2016: Blood
https://www.readbyqxmd.com/read/26941399/mir-181a-negatively-regulates-nf-%C3%AE%C2%BAb-signaling-and-affects-activated-b-cell-like-diffuse-large-b-cell-lymphoma-pathogenesis
#17
Goldi A Kozloski, Xiaoyu Jiang, Shruti Bhatt, Jose Ruiz, Francisco Vega, Rita Shaknovich, Ari Melnick, Izidore S Lossos
Distinct subgroups of diffuse large B-cell lymphoma (DLBCL) genetically resemble specific mature B-cell populations that are blocked at different stages of the immune response in germinal centers (GCs). The activated B-cell (ABC)-like subgroup resembles post-GC plasmablasts undergoing constitutive survival signaling, yet knowledge of the mechanisms that negatively regulate this oncogenic signaling remains incomplete. In this study, we report that microRNA (miR)-181a is a negative regulator of nuclear factor κ-light-chain enhancer of activated B-cells (NF-κB) signaling...
June 9, 2016: Blood
https://www.readbyqxmd.com/read/26603838/active-ikk%C3%AE-promotes-the-stability-of-gli1-oncogene-in-diffuse-large-b-cell-lymphoma
#18
Nitin K Agarwal, Chae H Kim, Kranthi Kunkalla, Hiroyasu Konno, Youley Tjendra, Deukwoo Kwon, Marzenna Blonska, Goldi A Kozloski, Vincent T Moy, Ramiro E Verdun, Glen N Barber, Izidore S Lossos, Francisco Vega
GLI1 oncogene has been implicated in the pathobiology of several neoplasms including diffuse large B-cell lymphoma (DLBCL). However, mechanisms underlying GLI1-increased activity in DLBCL are poorly characterized. Herein, we demonstrate that IKKβ phosphorylates GLI1 in DLBCL. IKKβ activation increased GLI1 protein levels and transcriptional activity, whereas IKKβ silencing decreased GLI1 levels and transcriptional activity. Tumor necrosis factor-α (TNFα) mediated IKKβ activation-impaired GLI1 binding with the E3 ubiquitin ligase-ITCH, leading to decreased K48-linked ubiquitination/degradation of GLI1...
February 4, 2016: Blood
https://www.readbyqxmd.com/read/26194763/direct-and-immune-mediated-cytotoxicity-of-interleukin-21-contributes-to-antitumor-effects-in-mantle-cell-lymphoma
#19
Shruti Bhatt, Julie Matthews, Salma Parvin, Kristopher A Sarosiek, Dekuang Zhao, Xiaoyu Jiang, Elif Isik, Anthony Letai, Izidore S Lossos
Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma characterized by overexpression of cyclin D1 in 95% of patients. MCL patients experience frequent relapses resulting in median survival of 3 to 5 years, requiring more efficient therapeutic regimens. Interleukin (IL)-21, a member of the IL-2 cytokine family, possesses potent antitumor activity against a variety of cancers not expressing the IL-21 receptor (IL-21R) through immune activation. Previously, we established that IL-21 exerts direct cytotoxicity on IL-21R-expressing diffuse large B-cell lymphoma cells...
September 24, 2015: Blood
https://www.readbyqxmd.com/read/26049758/lymphomirs-micrornas-with-regulatory-roles-in-lymphomas
#20
Goldi A Kozloski, Izidore S Lossos
PURPOSE OF REVIEW: This review provides current knowledge on the role of microRNAs (miRNAs) in lymphoma with an emphasis on mature B-cell lymphoma. RECENT FINDINGS: Although miRNAs were previously used to stratify lymphoma classification, prognosis, or treatment response, recent publications portray this class of small noncoding RNAs as critical players in the lymphomagenesis process. Although functional studies provide ample evidence for their role as lymphoma drivers or suppressors, genetic studies providing the underlying mechanisms for these phenotypes are still lacking...
July 2015: Current Opinion in Hematology
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