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Waldenstrom macroglobulinemia

Antonella Caivano, Francesco La Rocca, Vittorio Simeon, Marco Girasole, Simone Dinarelli, Ilaria Laurenzana, Angelo De Stradis, Luciana De Luca, Stefania Trino, Antonio Traficante, Giovanni D'Arena, Giovanna Mansueto, Oreste Villani, Giuseppe Pietrantuono, Luca Laurenti, Luigi Del Vecchio, Pellegrino Musto
PURPOSE: The use of extracellular vesicles (EVs) from body fluids as "liquid biopsies" is emerging as a promising approach for the diagnosis, prognosis and therapeutic monitoring of cancer patients. MicroRNA-155 (miR155), a non-coding transcript of the B-cell integration cluster (BIC) gene, has been reported to play a critical role in the pathogenesis of several types of hematologic malignancies (HMs) in which high miR155 levels have been found. At yet, however, the EV miR155 level and its putative clinical relevance in sera of HM patients have not been reported...
October 19, 2016: Cellular Oncology (Dordrecht)
Monique C Minnema, Eva Kimby, Shirley D'Sa, Luc-Matthieu Fornecker, Stéphanie Poulain, Tom J Snijders, Efstathios Kastritis, Stéphane Kremer, Aikaterini Fitsiori, Laurence Simon, Frédéric Davi, Michael Lunn, Jorge J Castillo, Christopher J Patterson, Magali Le Garff-Tavernier, Myrto Costopoulos, Véronique Leblond, Marie-José Kersten, Meletios A Dimopoulos, Steven P Treon
Bing Neel syndrome is a rare disease manifestation of Waldenstrom macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline, we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and include headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenstrom macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients...
October 6, 2016: Haematologica
Christina Kalpadakis, Gerassimos A Pangalis, Theodoros P Vassilakopoulos, Maria Roumelioti, Sotirios Sachanas, Penelope Korkolopoulou, Efstathios Koulieris, Maria Moschogiannis, Xanthi Yiakoumis, Pantelis Tsirkinidis, Charalampos Pontikoglou, Dimitra Rondoyianni, Helen A Papadaki, Panayiotidis Panayiotidis, Maria K Angelopoulou
Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM...
October 13, 2016: Hematological Oncology
Mohammed Shafi A, Chandilya Sc, Prabu P
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Maria Gavriatopoulou, Efstathios Kastritis, Marie-Christine Kyrtsonis, Theodoros P Vassilakopoulos, Maria Roussou, Despoina Fotiou, Magdalini Migkou, Maria Mpakiri, Anna Tasidou, Evangelos Terpos, Meletios Athanasios Dimopoulos
No abstract text is available yet for this article.
October 10, 2016: Leukemia & Lymphoma
Sang-Yong Shin, Seung-Tae Lee, Hyun-Young Kim, Chang-Hun Park, Hee-Jin Kim, Jong-Won Kim, Seok Jin Kim, Won Seog Kim, Sun-Hee Kim
BACKGROUND: Recent studies have identified a high prevalence of the MYD88 L265P mutation in lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) cases, whereas low frequencies have been observed in other B cell non-Hodgkin lymphomas (NHLs). METHODS: We evaluated the sensitivity of the mutant enrichment 3'-modified oligonucleotide (MEMO)-PCR technique, a new detection method. We examined the MYD88 L265P mutation in a series of Korean patients with LPL/WM and other B cell NHLs in bone marrow aspirates, using the MEMO-PCR technique...
September 2016: Blood Research
Koh Okamoto, Laurie A Proia, Patricia L Demarais
Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation...
2016: Case Reports in Infectious Diseases
Prashant Kapoor, Stephen M Ansell, Esteban Braggio
Waldenström macroglobulinemia (WM) is a rare, indolent, and monoclonal immunoglobulin M-associated lymphoplasmacytic disorder with unique clinicopathologic characteristics. Over the past decade, remarkable progress has occurred on both the diagnostic and therapeutic fronts in WM. A deeper understanding of the disease biology emanates from the seminal discoveries of myeloid differentiation primary response 88 (MYD88) L265P somatic mutation in the vast majority of cases and C-X-C chemokine receptor, type 4, mutations in about a third of patients...
2016: Cancer Treatment and Research
C I E Smith
BTK is a cytoplasmic protein-tyrosine kinase, whose corresponding gene was isolated in the early 1990s. BTK was initially identified by positional cloning of the gene causing X-linked agammaglobulinemia and independently in a search for new kinases. Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity...
September 26, 2016: Oncogene
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Robert Roskoski
The Bruton non-receptor protein-tyrosine kinase (BTK), a deficiency of which leads to X-linked agammaglobulinemia, plays a central role in B cell antigen receptor signaling. Owing to the exclusivity of this enzyme in B cells, the acronym could represent B cell tyrosine kinase. BTK is activated by the Lyn and SYK protein kinases following activation of the B cell receptor. BTK in turn catalyzes the phosphorylation and activation of phospholipase Cγ2 leading to the downstream activation of the Ras/RAF/MEK/ERK pathway and the NF-κB pathways...
September 15, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
H Y Ouyang, Z J Yu, J Yin, X J Zhao, Z Y Wang, W Zhang, Z N Ma, J Su, X Bai, C G Ruan
OBJECTIVE: To deepen the understanding of acquired von Willebrand syndrome (AVWS). METHODS: The clinical data of 3 patients were analyzed and related literature were reviewed. RESULTS: ① Case 1, a 70- year- old male, diagnosed as Waldenstrom macroglobulinemia and AVWS, was presented with spontaneous epitaxis and bruising. The VWF∶Ag level was 16%. Treatment was initiated with VWF concentrates. Two cycles of chemotherapy with Bortezomib, thalidomide and Dexamethasone were followed...
August 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Richard Rosenquist, Andreas Rosenwald, Ming-Qing Du, Gianluca Gaidano, Patricia Groenen, Andrew Wotherspoon, Paolo Ghia, Philippe Gaulard, Elias Campo, Kostas Stamatopoulos
Similar to the inherent clinical heterogeneity of most, if not all, lymphoma entities, the genetic landscape of these tumors is markedly complex in the majority of cases, with a rapidly growing list of recurrently mutated genes discovered in recent years by next-generation sequencing technology. Whilst a few genes have been implied to have diagnostic, prognostic and even predictive impact, most gene mutations still require rigorous validation in larger, preferably prospective patient series, to scrutinize their potential role in lymphoma diagnostics and patient management...
September 2016: Haematologica
Jorge J Castillo, Joshua N Gustine, Kirsten Meid, Toni Dubeau, Guang Yang, Lian Xu, Zachary R Hunter, Steven P Treon
No abstract text is available yet for this article.
August 26, 2016: Leukemia & Lymphoma
Jorge J Castillo, Morie A Gertz
In recent years, the survival of patients with plasma cell dyscrasias has improved due to improvements in anticancer and supportive therapy. However, the risk of secondary malignancies has increased, thought to be due to a combination of environmental and disease-related factors, as well as treatment. In the present review, we evaluate the risk of secondary malignancies in patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenström macroglobulinemia (WM). Patients with MGUS appear to have a higher risk of developing myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)...
August 22, 2016: Leukemia & Lymphoma
Jorge J Castillo, M Lia Palomba, Ranjana Advani, Steven P Treon
Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenström macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events...
August 2016: Therapeutic Advances in Hematology
Adam J Olszewski, Steven P Treon, Jorge J Castillo
INTRODUCTION: Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM) is a rare lymphoma affecting older patients. Its management largely relies on small phase II trials and it is unclear how their results translate into clinical practice in the community. METHOD: We evaluated changes in the presentation, management, and survival among 2,666 Medicare beneficiaries diagnosed with WM between 1994 and 2011, using Medicare claims linked to Surveillance, Epidemiology and End Results data...
July 29, 2016: Oncologist
James Q Wang, Bruce Beutler, Christopher C Goodnow, Keisuke Horikawa
The MYD88(L265P) mutation is found in 2% to 10% of chronic lymphocytic leukemia, 29% of activated B-cell type diffuse large B-cell lymphoma and 90% of Waldenström macroglobulinemia, making it conceptually attractive to treat these malignancies with inhibitors of endosomal Toll-like receptors (TLR9, TLR7) that activate MYD88. Here we show that genetic inhibition of endosomal TLRs has the opposite effect on accumulation of MYD88(L265P) B cells in vitro and in vivo. Activated mature B cells from wild-type, Unc93b1(3d/3d)-mutant, or Tlr9-deficient mice were transduced with retrovirus encoding MYD88(L265P) and analyzed either in vitro or after transplantation into Rag1(-/-) recipient mice...
September 22, 2016: Blood
Véronique Leblond, Efstathios Kastritis, Ranjana Advani, Stephen M Ansell, Christian Buske, Jorge J Castillo, Ramón García-Sanz, Morie Gertz, Eva Kimby, Charalampia Kyriakou, Giampaolo Merlini, Monique C Minnema, Pierre Morel, Enrica Morra, Mathias Rummel, Ashutosh Wechalekar, Christopher J Patterson, Steven P Treon, Meletios A Dimopoulos
Waldenström macroglobulinemia (WM) is a distinct B-cell lymphoproliferative disorder for which clearly defined criteria for the diagnosis, initiation of therapy, and treatment strategy have been proposed as part of the consensus panels of the International Workshop on Waldenström's Macroglobulinemia (IWWM). At IWWM-8, a task force for treatment recommendations was impanelled to review recently published and ongoing clinical trial data as well as the impact of new mutations (MYD88 and CXCR4) on treatment decisions, indications for B-cell receptor and proteasome inhibitors, and future clinical trial initiatives for WM patients...
September 8, 2016: Blood
A Santos-Lozano, A Morales-Gonzalez, F Sanchis-Gomar, C Cristi-Montero, C Fiuza-Luces, H Pareja-Galeano, J Martínez-López, N Garatachea, A Lucia
Waldenström macroglobulinemia (WM) is a malignant lymphoproliferative disorder characterized by the presence of a high level of serum monoclonal IgM and a lymphoplasmacytic infiltrate in the bone marrow. This meta-analysis sought to assess the effectiveness of the different treatments for WM tested in published trials using the response rate (RR) as the main outcome measure. Forty-six articles (1409 patients) identified were entered in a variable effects model meta-analysis of proportions (rates and sample sizes)...
September 2016: Critical Reviews in Oncology/hematology
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