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MYD88 and Lymphoma

Morie A Gertz
DISEASE OVERVIEW: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. DIAGNOSIS: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in >90% of patients and is found in the majority of IgM monoclonal gammopathy of undetermined significance patients...
October 17, 2018: American Journal of Hematology
Yang Liu, Yuanhang Liu, Xuecheng Huang, Jingchang Zhang, Lihui Yang
OBJECTIVE: Coronary microembolization (CME) is a common complication during the percutaneous coronary intervention (PCI). CME-induced local myocardial inflammation and myocardial apoptosis are the primary causes of progressive cardiac dysfunction. Curcumin exerts a protective role in various cardiovascular diseases; however, its effects in CME are yet to be clarified. Therefore, the current study investigated the effects of curcumin on myocardial inflammatory responses, myocardial apoptosis, and cardiac dysfunctions induced by CME in rats...
October 15, 2018: Journal of Cellular Biochemistry
Kerstin Wenzl, Michelle K Manske, Vivekananda Sarangi, Yan W Asmann, Patricia T Greipp, Hanna R Schoon, Esteban Braggio, Matthew J Maurer, Andrew L Feldman, Thomas E Witzig, Susan L Slager, Stephen M Ansell, James R Cerhan, Anne J Novak
MYD88 mutations are one of the most recurrent mutations in hematologic malignancies. However, recent mouse models suggest that MYD88L265P alone may not be sufficient to induce tumor formation. Interplay between MYD88L265P and other genetic events is further supported by the fact that TNFAIP3 (A20) inactivation often accompanies MYD88L265P . However, we are still lacking information about the consequence of MYD88L265P in combination with TNFAIP3 loss in human B cell lymphoma. Review of our genetic data on diffuse large B cell lymphoma (DLBCL) and Waldenstrom macroglobulinemia (WM), found that a large percentage of DLBCL and WM cases that have a MYD88 mutation also harbor a TNFAIP3 loss, 55% DLBCL and 28% of WM, respectively...
October 9, 2018: Blood Cancer Journal
Soheil Zorofchian, Guangrong Lu, Jay-Jiguang Zhu, Dzifa Y Duose, Justin Windham, Yoshua Esquenazi, Leomar Y Ballester
Primary Central Nervous System Lymphoma (PCNSL) and Metastatic (or Secondary) Central Nervous System Lymphoma (MCNSL) are rare central nervous system (CNS) malignancies that exhibit aggressive clinical behavior and have a poor prognosis. The majority of CNS lymphomas are histologically classified as diffuse large-B cell lymphoma (DLBCL). DLBCL harbors a high frequency of mutations in MYD88 and CD79b . The MYD88 p.L265P mutation occurs at high frequency in CNS lymphoma and is extremely rare in non-hematologic malignancies...
2018: Frontiers in Oncology
Huiying Qiu, Shenglan Gong, Lili Xu, Hui Cheng, Lei Gao, Jie Chen, Xiaoxia Hu, Jianmin Yang
The myeloid differentiation factor 88 (MYD88) signaling plays critical roles in the developments of B cells. Recent studies demonstrated that in the activated B cell subtype of diffuse large B cell lymphoma (DLBCL), approximately one-third of the patients harbored somatically acquired MyD88 L265P mutation in their lymphomas. It remains unclear whether B cell lymphomas with MYD88 L265P mutation respond differently toward CD8+ T cell-mediated cytotoxicity. Here, we demonstrated that, when incubated with autologous CD8+ T cells, the MYD88 L265P mutant lymphomas were more resistant to granzyme B- and perforin-mediated killing than MYD88 wild-type (WT) lymphomas...
September 22, 2018: International Immunopharmacology
Macha Samba-Mondonga, Annie Calvé, Frédérick A Mallette, Manuela M Santos
The myeloid differentiation primary response gene 88 (MyD88) is an adaptive protein that is essential for the induction of inflammatory cytokines through almost all the Toll-like receptors (TLRs). TLRs recognize molecular patterns present in microorganisms called pathogen-associated molecular patterns. Therefore, MyD88 plays an important role in innate immunity since its activation triggers the first line of defense against microorganisms. Herein, we describe the first reported role of MyD88 in an interconnection between innate immunity and the iron-sensing pathway (BMP/SMAD4)...
2018: Frontiers in Cell and Developmental Biology
Yangying Zhou, Wei Liu, Zhijie Xu, Hong Zhu, Desheng Xiao, Weiping Su, Ruolan Zeng, Yuhua Feng, Yumei Duan, Jianhua Zhou, Meizuo Zhong
Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery, radiotherapy, and chemotherapy. However, the outcome is poor because of its high invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next-generation sequencing (NGS) to detect 64 candidate genes. We used immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS showed that recurrent mutations in KMT2D and CD79B, components of the NF-κB pathway, accounted for 65% of total mutations in PCNSL samples...
October 2018: Neoplasia: An International Journal for Oncology Research
Anna Raimbault, Sigrid Machherndl-Spandl, Raphaël Itzykson, Sylvain Clauser, Nicolas Chapuis, Stéphanie Mathis, Jeroen Lauf, Anne-Sophie Alary, Barbara Burroni, Olivier Kosmider, Michaela Fontenay, Marie C Béné, Françoise Durrieu, Peter Bettelheim, Valérie Bardet
The diagnosis of Waldenström Macroglobulinaemia (WM)/lymphoplasmacytic lymphoma (LPL) remains one of exclusion because other B-cell lymphoproliferative disorders (B-LPD), such as marginal zone lymphoma (MZL), can fulfil similar criteria, including MYD88 L265P mutation. It has been suggested that expression of the myeloid marker CD13 (also termed ANPEP) is more frequent in LPL than in other B-LPD and has also been described on normal and malignant plasma cells. Here, CD13 expression was tested in a cohort of 1037 B-LPD patients from 3 centres by flow cytometry...
September 10, 2018: British Journal of Haematology
Marion Magierowicz, Cécile Tomowiak, Xavier Leleu, Stéphanie Poulain
Waldenström macroglobulinemia is a rare indolent B-cell lymphoma. Whole-exome sequencing studies have improved our knowledge of the Waldenström macroglobulinemia mutational landscape. The MYD88 L265P mutation is present in nearly 90% of patients with Waldenström macroglobulinemia. CXCR4 mutations are identified in approximately 30% of MYD88L265P cases and have been associated with ibrutinib resistance in clinical trials. Mutations in CD79B, ARID1a, or TP53 were described at lower frequency. Deciphering the earliest initiating lesions and identifying the molecular alterations leading to disease progression currently represent important goals in the future to identify the most relevant targets for precision therapy in Waldenström macroglobulinemia...
October 2018: Hematology/oncology Clinics of North America
Soheil Zorofchian, Hanadi El-Achi, Yuanqing Yan, Yoshua Esquenazi, Leomar Y Ballester
PURPOSE: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that affects the central nervous system (CNS). Although previous studies have reported the most common mutated genes in PCNSL, including MYD88 and CD79b, our understanding of genetic characterizations in primary CNS lymphomas is limited. The aim of this study was to perform a retrospective analysis investigating the most frequent mutation types, and their frequency, in PCNSL. METHODS: Fifteen patients with a diagnosis of PCNSL from our institution were analyzed for mutations in 406 genes and rearrangements in 31 genes by next generation sequencing (NGS)...
August 31, 2018: Journal of Neuro-oncology
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...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Valerie Touitou, Myrto Costopoulos, Karim Maloum
No abstract text is available yet for this article.
October 1, 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...
October 1, 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...
October 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) signalling 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 subtypes of DLBCL, known as germinal centre B cell-like and activated B cell-like (ABC)2,3 , that show poor outcomes after immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase signalling cascade of SYK, BTK and PKCβ to promote the assembly of the CARD11-BCL10-MALT1 adaptor complex, which recruits and activates IκB kinase4-6 ...
August 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
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