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MYD88 and Lymphoma

Wataru Munakata, Kiyoshi Ando, Kiyohiko Hatake, Noriko Fukuhara, Tomohiro Kinoshita, Suguru Fukuhara, Yukari Shirasugi, Masahiro Yokoyama, Satoshi Ichikawa, Ken Ohmachi, Naokazu Gion, Arata Aoi, Kensei Tobinai
We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics, and predictive biomarkers of tirabrutinib, a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-cell NHL) and chronic lymphocytic leukemia (CLL). This was an open-label, multicenter, phase I study. Seventeen patients (male N=8) with a median age of 70 years were enrolled in four dose cohorts (160 mg once daily [N=3], 320 mg once daily [N=3], 480 mg once daily [N=4], and 300 mg twice daily [N=7]); four patients had continued tirabrutinib administration as of January 4, 2018...
February 27, 2019: Cancer Science
Laura Fogliatto, Kamila Castro Grokoski, Yuri Machado Strey, Tito Vanelli, Christina Garcia da Silva Fraga, Marines Bizarro Barra, Fernanda Correa Pinto, Israel Bendit, Claúdia Giuliano Bica
Background: Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population. Objective: The main objective of this retrospective study was to assess the impact of tumor markers, including the Myeloid differentiation primary response 88 (MYD88) mutation. Method: Eighty-three patients were included and treated with R-CHOP or R-CHOP-like regimens...
January 2019: Hematology, Transfusion and Cell Therapy
Shao-Hua Tian, De-Jun Yu, Zhi-Yong Li, Wen-Long Zhang
Ischemia reperfusion injury (IRI), a complex phenomenon often encountered in surgery, can lead to local and distant tissue destruction and sometimes even death. microRNA-203 (miR-203) has been reported to negatively regulate ischemia induced microglia activation with a feedback to myeloid differentiation primary-response gene 88 (MYD88). Accordingly, our study is to verify the effect of miR-203 and MYD88 on mice in IRI after total knee arthroplasty (TKA). After establishment of IRI mouse model, heart rate (HR) and mean arterial pressure (MAP) in mice were determined...
February 14, 2019: Gene
Naema Nayyar, Michael D White, Corey M Gill, Matthew Lastrapes, Mia Bertalan, Alexander Kaplan, Megan R D'Andrea, Ivanna Bihun, Andrew Kaneb, Jorg Dietrich, Judith A Ferry, Maria Martinez-Lage, Anita Giobbie-Hurder, Darrell R Borger, Fausto J Rodriguez, Matthew P Frosch, Emily Batchelor, Kaitlin Hoang, Benjamin Kuter, Sarah Fortin, Matthias Holdhoff, Daniel P Cahill, Scott Carter, Priscilla K Brastianos, Tracy T Batchelor
The genetic alterations that define primary central nervous system lymphoma (PCNSL) are incompletely elucidated, and the genomic evolution from diagnosis to relapse is poorly understood. We performed whole-exome sequencing (WES) on 36 PCNSL patients and targeted MYD88 sequencing on a validation cohort of 27 PCNSL patients. We also performed WES and phylogenetic analysis of 3 matched newly diagnosed and relapsed tumor specimens and 1 synchronous intracranial and extracranial relapse. Immunohistochemistry (IHC) for programmed death-1 ligand (PD-L1) was performed on 43 patient specimens...
February 12, 2019: Blood Advances
Sarah Menguy, Marie Beylot-Barry, Parrens Marie, Anne Pham Ledard, Eric Frison, François Comoz, Maxime Battistella, Vanessa Szablewski, Brigitte Balme, Anne Croue, Frédéric Franck, Nicolas Ortonne, Emilie Tournier, Laurence Lamant, Agnès Carlotti, Anne De Muret, François Le Gall, Marie-Hélène Lorton, Jean-Philippe Merlio, Béatrice Vergier
AIMS: We applied the 2017 WHO classification criteria to categorize a series of 64 primary cutaneous large B-cell lymphomas (PCLBCLs), containing a majority (⩾80%) of large-cells and a proliferative rate ⩾40%, raising the problem of the differential diagnosis between PCLBCLs, leg type (PCLBCLs-LT) or primary cutaneous follicle center lymphomas with large cell morphology (PCFCLs-LC). The aims were to determine reproducibility and prognostic relevance of the 2017 WHO criteria. METHODS AND RESULTS: Morphology and phenotype identified 32 PCLBCLs-LT and 25 PCFCLs-LC; 7 cases (11%) remained unclassified...
February 4, 2019: Histopathology
Keisuke Kataoka, Hiroaki Miyoshi, Seiji Sakata, Akito Dobashi, Lucile Couronné, Yasunori Kogure, Yasuharu Sato, Kenji Nishida, Yuka Gion, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Chiba, Yosaku Watatani, Nobuyuki Kakiuchi, Yusuke Shiozawa, Tetsuichi Yoshizato, Kenichi Yoshida, Hideki Makishima, Masashi Sanada, Masahiro Onozawa, Takanori Teshima, Yumiko Yoshiki, Tadao Ishida, Kenshi Suzuki, Kazuyuki Shimada, Akihiro Tomita, Motohiro Kato, Yasunori Ota, Koji Izutsu, Ayako Demachi-Okamura, Yoshiki Akatsuka, Satoru Miyano, Tadashi Yoshino, Philippe Gaulard, Olivier Hermine, Kengo Takeuchi, Koichi Ohshima, Seishi Ogawa
Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic aberrations in 384 samples from various lymphoma subtypes using high-throughput sequencing, particularly focusing on virus-associated lymphomas. A high frequency of PD-L1/PD-L2-involving genetic aberrations was observed in EBV-positive lymphomas [33 (22%) of 148 cases], including extranodal NK/T-cell lymphoma (ENKTL, 23%), aggressive NK-cell leukemia (57%), systemic EBV-positive T-cell lymphoproliferative disorder (17%) as well as EBV-positive diffuse large B-cell lymphoma (DLBCL, 19%) and peripheral T-cell lymphoma-not otherwise specified (15%)...
January 25, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
V Kakkassery, A M Jünemann, B O Scheef, S Grisanti, L M Heindl
BACKGROUND: Molecular pathological research offers new chances for the diagnostic and therapeutic management of malignant iris tumors. Besides immunohistological and polymerase chain reaction analyses further techniques, such as multiplex ligation-dependent probe amplification, microsatellite analyses and next-generation sequencing are able to detect various mutations in the tumor genome. OBJECTIVE: An up to date review of new molecular pathological strategies for malignant iris tumors was carried out...
January 8, 2019: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
Xiaoyan Yuan, Jinyuan Zhu, Qi Kang, Xiaoxue He, Dongfeng Guo
BACKGROUND Sepsis-induced lung injury is associated with high mortality. The present investigation evaluated the protective effect of hesperidin against sepsis-induced lung injury and also postulates the possible mechanism of its action. MATERIAL AND METHODS Lung injury was induced by sepsis in all animals, in which sepsis was produced by cecal ligation and puncture (CLP). Animals were treated with hesperidin 10 and 20 mg/kg i.v. 30 min after the surgery. Oxygenation index and lung injury score were determined and levels of pro-inflammatory mediators and markers of oxidative stress were also estimated in the lung tissues...
January 4, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Zi-Xuan Ding, Hong Liu, Jun-Dan Xie, Hong Yao, Liang Ma, Qiao-Chen Qiu, Hong-Jie Shen
OBJECTIVE: To investigate the feasibility of sensitive and quantitative detection of MYD88 gene L265P mutation in lymphoma patients by using ARMS-PCR combined with capillary electrophoresis. METHODS: ARMS-PCR amplified MYD88 gene was analyzed by capillary electrophoresis in ABI 3730 sequencer; Exon 5 of the same gene was sequenced bi-directionally as reported. RESULTS: The sensitivity of detection L265P mutations by the ARMS-PCR combined with capillary electrophoresis and direct sequencing was 0...
December 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Amir Behdad, Xiao Yi Zhou, Juehua Gao, Kirtee Raparia, David Dittman, Stefan J Green, Chao Qi, Bryan Betz, Paul Bryar, Qing Chen, Yi-Hua Chen
CONTEXT.—: The pathogenesis of primary ocular adnexal marginal zone lymphoma (POAMZL) remains unclear. The reported associations with Chlamydia psittaci infection and MYD88 mutations are highly variable. OBJECTIVE.—: To examine MYD88 L265P mutation in ocular marginal zone lymphomas and correlate with clinicopathologic features and Chlamydia infection. DESIGN.—: Presence of MYD88 L265P mutation and Chlamydia infection in lymphoma was analyzed by using sensitive polymerase chain reaction (PCR) methods...
November 16, 2018: Archives of Pathology & Laboratory Medicine
Patrizia Mondello, Elliott J Brea, Elisa De Stanchina, Eneda Toska, Aaron Y Chang, Myles Fennell, Venkatraman Seshan, Ralph Garippa, David A Scheinberg, José Baselga, Hans-Guido Wendel, Anas Younes
No abstract text is available yet for this article.
November 15, 2018: JCI Insight
Zachary R Hunter, Lian Xu, Nickolas Tsakmaklis, Maria G Demos, Amanda Kofides, Cristina Jimenez, Gloria G Chan, Jiaji Chen, Xia Liu, Manit Munshi, Joshua Gustine, Kirsten Meid, Christopher J Patterson, Guang Yang, Toni Dubeau, Mehmet K Samur, Jorge J Castillo, Kenneth C Anderson, Nikhil C Munshi, Steven P Treon
Activating MYD88 mutations are present in 95% of Waldenström macroglobulinemia (WM) patients, and trigger NF-κB through BTK and IRAK. The BTK inhibitor ibrutinib is active in MYD88- mutated (MYD88 MUT ) WM patients, but shows lower activity in MYD88 wild-type ( MYD88 WT ) disease. MYD88 WT patients also show shorter overall survival, and increased risk of disease transformation in some series. The genomic basis for these findings remains to be clarified. We performed whole exome and transcriptome sequencing of sorted tumor samples from 18 MYD88 WT patients and compared findings with WM patients with MYD88 MUT disease...
November 13, 2018: Blood Advances
Cora Hallas, Michael Preukschas, Markus Tiemann
Gene expression profiling (GEP) separated diffuse large B-cell lymphoma (DLBCL) in two different entities, i.e. activated B cell-like (ABC) and germinal center B cell-like (GCB) lymphomas with ABC lymphomas demonstrating a less favorable outcome. NF-kB pathway activating mutations in MYD88, CD79A/B and CARD11 are predominantly found in ABC type lymphomas. Targeted therapies affecting NF-kB pathways have shown therapeutic potential in this subtype. Immunohistochemistry algorithms have been developed as a tool for distinguishing these entities in routine clinical diagnostics...
January 2019: Leukemia Research
Jan Devan, Andrea Janikova, Marek Mraz
The molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain enhancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2, CBP/CREBBP, p300/EP300, and HIST1H1 in >95% of cases...
October 2018: Seminars in Oncology
Keiichiro Hattori, Mamiko Sakata-Yanagimoto, Manabu Kusakabe, Toru Nanmoku, Yasuhito Suehara, Ryota Matsuoka, Masayuki Noguchi, Yasuhisa Yokoyama, Takayasu Kato, Naoki Kurita, Hidekazu Nishikii, Naoshi Obara, Shingo Takano, Eiichi Ishikawa, Akira Matsumura, Masafumi Muratani, Yuichi Hasegawa, Shigeru Chiba
Primary central nervous system lymphoma (PCNSL) is a rare subtype of lymphoma that arises within the brain or the eyes. PCNSL recurs within the central nervous system (CNS) in most relapsed cases, whereas extra-CNS relapse is experienced in rare cases. The present study aimed at identifying the presence of common precursor cells (CPC) for primary intra- and relapsed extra-CNS tumors, and further assessing the initiating events in bone marrow (BM). Targeted deep sequencing was carried out for five paired primary intra- and relapsed extra-CNS tumors of PCNSL...
October 24, 2018: Cancer Science
Kuixing Zhang, Daniel Farrell, Deepa Jeyakumar, Susan O'Brien, Xiaohui Zhao, Sherif A Rezk
Although rare cases of prolymphocytic transformation from splenic B-cell lymphomas and follicular lymphoma have been reported, prolymphocytic transformation from lymphoplasmacytic lymphoma has not been previously reported. We report a case of 76-year old male patient with a history of Waldenström's Macroglobulinemia diagnosed in 2010 and treated with infusion chemotherapy. He was in clinical remission for 5years. In 2016, he presented with diffuse lymphadenopathy and a head and neck lymph node biopsy showed lymphoplasmacytic lymphoma...
October 17, 2018: Human Pathology
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
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