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Lossos Izidore

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 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, 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...
October 27, 2016: Blood
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)...
September 21, 2016: Leukemia & Lymphoma
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
Juan Pablo Alderuccio, Pooja Amarapurkar, Jennifer R Chapman, Francisco Vega, Izidore S Lossos
No abstract text is available yet for this article.
June 2, 2016: Leukemia & Lymphoma
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
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
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
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
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
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
Andrew M Evens, Jennifer A Kanakry, Laurie H Sehn, Athena Kritharis, Tatyana Feldman, Aimee Kroll, Randy D Gascoyne, Jeremy S Abramson, Adam M Petrich, Francisco J Hernandez-Ilizaliturri, Zeina Al-Mansour, Camille Adeimy, Jessica Hemminger, Nancy L Bartlett, Anthony Mato, Paolo F Caimi, Ranjana H Advani, Andreas K Klein, Chadi Nabhan, Sonali M Smith, Jesus C Fabregas, Izidore S Lossos, Oliver W Press, Timothy S Fenske, Jonathan W Friedberg, Julie M Vose, Kristie A Blum
Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P = 0.0001); more often had bone marrow involvement (19% versus 0%, P = 0...
September 2015: American Journal of Hematology
Xiaoqing Lu, Renaud Sicard, Xiaoyu Jiang, Jessica N Stockus, George McNamara, Midhat Abdulreda, Vincent T Moy, Ralf Landgraf, Izidore S Lossos
Human germinal center-associated lymphoma (HGAL) is specifically expressed only in germinal center (GC) B lymphocytes and GC-derived lymphomas. HGAL protein decreases lymphocyte motility by inhibiting the ability of myosin to translocate actin via direct interaction with F-actin and myosin II and by activating RhoA signaling via direct interactions with RhoA-specific guanine nucleotide exchange factors. HGAL protein also regulates B-cell receptor (BCR) signaling by directly binding to and enhancing Syk kinase activity and activation of its downstream effectors...
January 22, 2015: Blood
Sampath Ramachandiran, Arsene Adon, Xiangxue Guo, Yi Wang, Huichen Wang, Zhengjia Chen, Jeanne Kowalski, Ustun R Sunay, Andrew N Young, Theresa Brown, Jessica C Mar, Yuhong Du, Haian Fu, Karen P Mann, Yasodha Natkunam, Lawrence H Boise, Harold I Saavedra, Izidore S Lossos, Leon Bernal-Mizrachi
Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma in the United States. DLBCL comprises biologically distinct subtypes including germinal center-like (GCB) and activated-B-cell-like DLBCL (ABC). The most aggressive type, ABC-DLBCL, displays dysregulation of both canonical and noncanonical NF-κB pathway as well as genomic instability. Although, much is known about the tumorigenic roles of the canonical NF-kB pathway, the precise role of the noncanonical NF-kB pathway remains unknown...
May 15, 2015: International Journal of Cancer. Journal International du Cancer
Izidore S Lossos, Jesus C Fabregas, Tulay Koru-Sengul, Feng Miao, Deborah Goodman, Aldo N Serafini, Peter J Hosein, Alexandra Stefanovic, Joseph D Rosenblatt, James E Hoffman
The best upfront therapy for patients with non-gastric extranodal marginal zone lymphomas (MZLs) is not defined. We assessed the safety and efficacy of radioimmunotherapy with (90)yttrium ((90)Y) ibritumomab tiuxetan as upfront therapy in MZL (NCT00453102). A total of 16 patients were enrolled, 81% with advanced-stage disease and 44% with bulky disease. The overall response rate (ORR) at 12 weeks post-therapy was 87.5% (90% confidence interval [CI]: 65.6-97.7%), including a complete response in eight (50%), complete response unconfirmed in one (6%) and partial response in five (31%) patients...
June 2015: Leukemia & Lymphoma
Jennifer Chapman-Fredricks, Jose Sandoval-Sus, Francisco Vega, Izidore S Lossos
Leukemic, non-nodal mantle cell lymphoma (MCL) is a relatively indolent disease characterized by asymptomatic leukemic presentation, non-nodal disease distribution, and slow disease progression, particularly in comparison to that of classic nodal MCL. We studied 3 cases of leukemic, non-nodal MCL in which TP53, ATM, and/or 13q14 deletions were identified. All three patients had disease progression leading to treatment requirements in two of the patients at 5 and 18 months after initial diagnosis. The third patient also clinically progressed 25 months after initial diagnosis but was lost to follow up despite recommendation for initiation of therapy...
August 2014: Annals of Diagnostic Pathology
Andrew M Evens, Mitchell R Smith, Izidore S Lossos, Irene Helenowski, Michael Millenson, Jane N Winter, Steve T Rosen, Leo I Gordon
There is a lack of published data examining non-cytotoxic options for the frontline treatment of patients with high-tumour burden (HTB) indolent non-Hodgkin lymphoma (iNHL). We completed a multicentre phase II study for patients with untreated HTB iNHL (NCT00369707) consisting of three induction cycles of weekly bortezomib and rituximab followed by an abbreviated consolidation. Forty-two patients were treated and all were evaluable; the most common histology was follicular lymphoma (FL) (n = 33, 79%). Patient characteristics included median age 62 years (40-86); 38% bulky disease; 19% malignant effusions; 91% advanced-stage disease; and median FL International Prognostic Index (FLIPI) score was 3...
August 2014: British Journal of Haematology
James Hoffman, Izidore S Lossos
No abstract text is available yet for this article.
September 2014: Leukemia & Lymphoma
Izidore S Lossos
No abstract text is available yet for this article.
March 13, 2014: Blood
Chen Lossos, Soley Bayraktar, Elizabeth Weinzierl, Sheren F Younes, Peter J Hosein, Robert J Tibshirani, Jocelyn Sutton Posthumus, Lisa M DeAngelis, Jeffrey Raizer, David Schiff, Lauren Abrey, Yasodha Natkunam, Izidore S Lossos
Primary central nervous system lymphoma (PCNSL) is an aggressive sub-variant of non-Hodgkin lymphoma (NHL) with morphological similarities to diffuse large B-cell lymphoma (DLBCL). While methotrexate (MTX)-based therapies have improved patient survival, the disease remains incurable in most cases and its pathogenesis is poorly understood. We evaluated 69 cases of PCNSL for the expression of HGAL (also known as GCSAM), LMO2 and BCL6 - genes associated with DLBCL prognosis and pathobiology, and analysed their correlation to survival in 49 PCNSL patients receiving MTX-based therapy...
June 2014: British Journal of Haematology
Peter J Hosein, Jocelyn C Maragulia, Matthew P Salzberg, Oliver W Press, Thomas M Habermann, Julie M Vose, Martin Bast, Ranjana H Advani, Robert Tibshirani, Andrew M Evens, Nahida Islam, John P Leonard, Peter Martin, Andrew D Zelenetz, Izidore S Lossos
Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on pathology and outcome. A multicentre retrospective study was undertaken to determine prognostic factors and the incidence of central nervous system (CNS) relapses. Data was retrospectively collected on patients from 8 US academic centres. Only patients with stage I/II disease (involvement of breast and localized lymph nodes) were included. Histologies apart from primary DLBCL were excluded...
May 2014: British Journal of Haematology
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