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MYD88 and Lymphoma

Lu Wang, Kewei Yu, Xiang Zhang, Shuwen Yu
The myeloid differentiation factor 88 (MyD88), an adaptor protein in regulation of the innate immunity, functions to regulate immune responses against viral and bacterial infections in the human body. Toll-like receptors (TLRs) and interleukin 1 receptors (IL-1R) can recognize microbes or endogenous ligands and then recruit MyD88 to activate the MyD88-dependent pathway, while MyD88 mutation associated with lymphoma development and altered MyD88 signaling also involved in cancer-associated cell intrinsic and extrinsic inflammation progression and carcinogenesis...
August 4, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Valerie Touitou, Myrto Costopoulos, Karim Maloum
No abstract text is available yet for this article.
July 19, 2018: JAMA Ophthalmology
Laura S Hiemcke-Jiwa, Ninette H Ten Dam-van Loon, Roos J Leguit, Stefan Nierkens, Jeannette Ossewaarde-van Norel, Joke H de Boer, Floor F Roholl, Roel A de Weger, Manon M H Huibers, Jolanda D F de Groot-Mijnes, Jonas J W Kuiper
Importance: The diagnostic workup of patients suspected of having vitreoretinal lymphoma (VRL) is primarily based on vitreous fluid analysis, including the recently emerging myeloid differentiation primary response gene 88 (MYD88) mutation analysis. Aqueous humor paracentesis is a relatively less invasive and safer procedure than taking vitreous fluid specimens, and aqueous humor-based MYD88 mutation analysis would provide an additional liquid biopsy tool to diagnose and monitor patients with VRL...
July 19, 2018: JAMA Ophthalmology
Elsa Maitre, Philippe Bertrand, Catherine Maingonnat, Pierre-Julien Viailly, Margaux Wiber, Dina Naguib, Véronique Salaün, Edouard Cornet, Gandhi Damaj, Brigitte Sola, Fabrice Jardin, Xavier Troussard
Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. BRAFV600E mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type BRAF gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies ( BRAF , MAP2K1 , DUSP2 , MAPK15 , ARID1A , ARID1B , EZH2 , KDM6A , CREBBP , TP53 , CDKN1B , XPO1 , KLF2 , CXCR4 , NOTH1 , NOTCH2 , MYD88 , ANXA1 , U2AF1 , BCOR , and ABCA8 )...
June 22, 2018: Oncotarget
Miyuki Abe, Masuho Saburi, Kazuhito Itani, Kazuhiro Kohno, Yasuhiro Soga, Yoshiyuki Kondo, Yawara Kawano, Toshiyuki Nakayama
A 76-year-old woman presented to our hospital with leukocytosis and abnormal lymphocytes. M protein of the immunoglobulin G (IgG) type was detected using immunoelectrophoresis. A bone marrow biopsy revealed infiltration of small mature lymphocytes, lymphoplasmacytoid cells with Dutcher bodies, grape cells, and Russell bodies. The MYD88 L265P mutation was detected in the abnormal peripheral lymphocytes, and a diagnosis of lymphoplasmacytoid lymphoma was established. MYD88 L265P mutation analysis is useful for making a diagnosis of non-IgM lymphoplasmacytoid lymphoma because it enables the differentiation from other low-grade B-cell malignancies...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Shunyou Gong, Genevieve M Crane, Chad M McCall, Wenbin Xiao, Karthik A Ganapathi, Nathan Cuka, Theresa Davies-Hill, Liqiang Xi, Mark Raffeld, Stefania Pittaluga, Amy S Duffield, Elaine S Jaffe
Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immunosuppression, suggesting that they should be considered as a form of posttransplant lymphoproliferative disorders. We identified 10 cases of EBV MZL, 9 in extranodal sites and 1 presenting in lymph node...
June 27, 2018: American Journal of Surgical Pathology
Yasuo Takashima, Yasushi Sasaki, Azusa Hayano, Jumpei Homma, Junya Fukai, Yasuo Iwadate, Koji Kajiwara, Shin Ishizawa, Hiroaki Hondoh, Takashi Tokino, Ryuya Yamanaka
Exome-sequencing for somatic mutation detection and copy number variation analysis are effective and valid methods for evaluating human cancers in current molecular medicine. We conducted target amplicon exome-sequencing analyses using PCR target enrichment and next-generation sequencing on Ion Proton semiconductor sequencers. Twenty-seven primary central nervous system lymphoma (PCNSL) specimens and their corresponding noncancerous tissues were used for multiplex PCR amplification to obtain targeted coverages of the entire coding regions of 409 cancer-related genes...
June 8, 2018: Oncotarget
Thomas A Ollila, Adam J Olszewski
Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement...
June 21, 2018: Current Treatment Options in Oncology
James D Phelan, Ryan M Young, Daniel E Webster, Sandrine Roulland, George W Wright, Monica Kasbekar, Arthur L Shaffer, Michele Ceribelli, James Q Wang, Roland Schmitz, Masao Nakagawa, Emmanuel Bachy, Da Wei Huang, Yanlong Ji, Lu Chen, Yandan Yang, Hong Zhao, Xin Yu, Weihong Xu, Maryknoll M Palisoc, Racquel R Valadez, Theresa Davies-Hill, Wyndham H Wilson, Wing C Chan, Elaine S Jaffe, Randy D Gascoyne, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Lisa M Rimsza, Fausto J Rodriguez, Fayez Estephan, Matthias Holdhoff, Michael J Kruhlak, Stephen M Hewitt, Craig J Thomas, Stefania Pittaluga, Thomas Oellerich, Louis M Staudt
B cell receptor (BCR) signaling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1 . Gene expression profiling identified two major DLBCL subtypes, known as germinal center (GC) B cell-like (GCB) and activated B cell-like (ABC)2,3 , with inferior outcomes following immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase cascade of SYK, BTK and PKCβ to promote the assembly of the CARD11-BCL10-MALT1 (CBM) adapter complex that recruits and activates IκB kinase (IKK)4-6 ...
June 20, 2018: Nature
Lucy C Fox, Costas K Yannakou, Georgina Ryland, Stephen Lade, Michael Dickinson, Belinda A Campbell, Henry Miles Prince
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p...
June 13, 2018: International Journal of Molecular Sciences
Andrew M Intlekofer, Erel Joffe, Connie L Batlevi, Patrick Hilden, Jie He, Venkatraman E Seshan, Andrew D Zelenetz, M Lia Palomba, Craig H Moskowitz, Carol Portlock, David J Straus, Ariela Noy, Steven M Horwitz, John F Gerecitano, Alison Moskowitz, Paul Hamlin, Matthew J Matasar, Anita Kumar, Marcel R van den Brink, Kristina M Knapp, Janine D Pichardo, Michelle K Nahas, Sally E Trabucco, Tariq Mughal, Amanda R Copeland, Elli Papaemmanuil, Mathai Moarii, Ross L Levine, Ahmet Dogan, Vincent A Miller, Anas Younes
We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma)...
June 12, 2018: Blood Cancer Journal
Laura S Hiemcke-Jiwa, Roos J Leguit, Tom J Snijders, N Mehdi Jiwa, Jonas J W Kuiper, Roel A de Weger, Monique C Minnema, Manon M H Huibers
Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma with a poor prognosis, for which accurate and timely diagnosis is of utmost importance. Unfortunately, diagnosis of PCNSL can be challenging and a brain biopsy (gold standard for diagnosis) is an invasive procedure with the risk of major complications. Thus, there is an urgent need for an alternative strategy to diagnose and monitor these lymphomas. Currently, liquid biopsies from cerebrospinal fluid (CSF) are used for cytomorphologic and flow cytometric analysis...
July 2018: Critical Reviews in Oncology/hematology
Christophe Boudesco, Els Verhoeyen, Laurent Martin, Catherine Chassagne-Clement, Leila Salmi, Rana Mhaidly, Céline Pangault, Thierry Fest, Selim Ramla, Fabrice Jardin, Olaf-Oliver Wolz, Alexander N R Weber, Carmen Garrido, Gaetan Jego
Activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) is an aggressive lymphoproliferative disorder involving chronic NF-κB activation. Several mutations in the BCR and MyD88 signaling pathway components, such as MyD88 L265P, are implicated in this aberrant activation. Among heat shock proteins, HSP110 has recently been identified as a prosurvival and/or proliferation factor in many cancers, but its role in ABC-DLBCL survival mechanisms remained to be established. We observed that short hairpin RNA-mediated HSP110 silencing decreased the survival of several ABC-DLBCL cell lines and decreased immunoglobulin M-MyD88 co-localization and subsequent NF-κB signaling...
August 2, 2018: Blood
N Cilla, M Vercruyssen, L Ameye, M Paesmans, A de Wind, P Heimann, N Meuleman, D Bron
INTRODUCTION: An IgM monoclonal gammopathy points to a diagnosis of Waldenstrom's Macroglobulinemia. Other B lymphoproliferatives disorders should be ruled out but the limits are sometimes difficult to define. The discovery of the L265P mutation of the MYD88 gene simplified potentially the situation. POPULATION AND METHODS: 383 patients of the Jules Bordet Institute with an IgM level above 2 g/L were reviewed. For the 49 who had a monoclonal peak, we analysed the underlying pathology in termes of general, clinical and biological characteristics...
May 30, 2018: Revue Médicale de Bruxelles
Jose S Pulido, Patrick B Johnston, Grzegorz S Nowakowski, Allessia Castellino, Harish Raja
Background: To describe the recent diagnostic and treatment options for the most predominant form of primary vitreoretinal lymphoma (PVRL), namely diffuse large B cell lymphoma. This is mainly based on the experience at the Mayo Clinic as well as a partial review of the literature. MYD88 L265P mutation is seen in about 80% of cases; therefore, a polymerase chain reaction for this mutation helps in making the diagnosis that has been notoriously difficult to make. Local therapy using intravitreal methotrexate and rituximab has been very helpful in the treatment of the local disease...
2018: International Journal of Retina and Vitreous
Vaishali Aggarwal, Ashim Das, Amanjit Bal, Radhika Srinivasan, Reena Das, Gaurav Prakash, Pankaj Malhotra, Subhash Varma
Diffuse large B-cell lymphoma (DLBCL) has a heterogenous biological behavior, and the western literature has reported activating oncogenic mutations in myeloid differentiation primary response gene 88 (MYD88), in conjunction with B-cell receptor signaling pathway genes, CARD11 and CD79B as the driving force for activating the NF-κB pathway implicated in the pathogenesis of DLBCL. The mutation profile of MYD88 genes was evaluated by Sanger sequencing in a cohort of 97 patients [DLBCL (N=55), non-DLBCL lymphomas (N=30), reactive lymphadenopathy (N=10), and 2 cases of lymphoplasmacytic lymphoma (positive control)]...
May 4, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Morie A Gertz
Waldenström macroglobulinemia is often an indolent disorder, and many patients are candidates for observation with careful monitoring. For symptomatic patients, one must distinguish between those patients whose symptoms are related to immunologic manifestations associated with the IgM monoclonal protein and those that have symptoms related to progressive marrow and nodal infiltration with lymphoplasmacytic lymphoma. In Waldenström macroglobulinemia, the driver for therapy in the majority of patients is progressive anemia, secondary to bone marrow replacement by lymphoplasmacytic lymphoma...
May 1, 2018: Blood Cancer Journal
Xinfang Yu, Wei Li, Qipan Deng, Ling Li, Eric D Hsi, Ken H Young, Mingzhi Zhang, Yong Li
Next-generation sequencing has revealed cancer genomic landscapes, in which over 100 driver genes that, when altered by intragenic mutations, can promote oncogenesis. MYD88 is a driver gene found in hematologic B-cell malignancies. A missense mutation (L265P) changing leucine at position 265 to proline in MYD88 is found in ∼90% of Waldenström macroglobulinemia (WM) cases and in significant portions of activated B-cell diffuse large B-cell lymphomas and IgM monoclonal gammopathy of undetermined significance...
May 15, 2018: Cancer Research
Daniela Drandi, Elisa Genuardi, Irene Dogliotti, Martina Ferrante, Cristina Jiménez, Francesca Guerrini, Mariella Lo Schirico, Barbara Mantoan, Vittorio Muccio, Giuseppe Lia, Gian Maria Zaccaria, Paola Omedè, Roberto Passera, Lorella Orsucci, Giulia Benevolo, Federica Cavallo, Sara Galimberti, Ramón García Sanz, Mario Boccadoro, Marco Ladetto, Simone Ferrero
We here describe a novel method for MYD88 L265P mutation detection and minimal residual disease monitoring in Waldenström macroglobulinemia, by droplet digital polymerase chain reaction, in bone marrow and peripheral blood cells, as well as in circulating cell-free DNA. Our method shows a sensitivity of 5.00×10-5 , which is far superior to the widely used allele-specific polymerase chain reaction (1.00×10-3 ). Overall, 291 unsorted samples from 148 patients (133 with Waldenström macroglobulinemia, 11 with IgG lymphoplasmacytic lymphoma and 4 with IgM monoclonal gammopathy of undetermined significance) were analyzed: 194 were baseline samples and 97 were followup samples...
June 2018: Haematologica
Anne M R Schrader, Patty M Jansen, Rein Willemze, Maarten H Vermeer, Anne-Marie Cleton-Jansen, Sebastiaan F Somers, Hendrik Veelken, Ronald van Eijk, Willem Kraan, Marie José Kersten, Michiel van den Brand, Wendy B C Stevens, Daphne de Jong, Myrurgia Abdul Hamid, Bea C Tanis, Eduardus F M Posthuma, Marcel Nijland, Arjan Diepstra, Steven T Pals, Arjen H G Cleven, Joost S P Vermaat
No abstract text is available yet for this article.
May 3, 2018: Blood
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