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MYD88 and Lymphoma

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...
October 10, 2018: 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 22, 2018: Seminars in Oncology
Keiichiro Hattori, Mamiko Sakata-Yanagimoto, Manabu Kusakabe, Tohru 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 CNS in most of relapsed cases, while 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 the bone marrow (BM). Targeted deep sequencing was performed for 5 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
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
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