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Biomarker mantle lymphoma

Carol L Shields, Jason L Chien, Thamolwan Surakiatchanukul, Kareem Sioufi, Sara E Lally, Jerry A Shields
Conjunctival tumors encompass a broad range of diagnoses. The 3 most important malignant tumors include ocular surface squamous neoplasia (OSSN) (14%), melanoma (12%), and lymphoma (7%). Conjunctival malignancies are rarely found in children. Regarding OSSN, pre-disposing conditions include chronic solar radiation, immune deficiency (HIV), organ transplant, autoimmune conditions, xeroderma pigmentosum, and chronic exposure to cigarette smoke. OSSN is managed surgically or with topical/injection immunotherapy or chemotherapy...
March 2017: Asia-Pacific Journal of Ophthalmology
David W Scott, Pau Abrisqueta, George W Wright, Graham W Slack, Anja Mottok, Diego Villa, Pedro Jares, Hilka Rauert-Wunderlich, Cristina Royo, Guillem Clot, Magda Pinyol, Merrill Boyle, Fong Chun Chan, Rita M Braziel, Wing C Chan, Dennis D Weisenburger, James R Cook, Timothy C Greiner, Kai Fu, German Ott, Jan Delabie, Erlend B Smeland, Harald Holte, Elaine S Jaffe, Christian Steidl, Joseph M Connors, Randy D Gascoyne, Andreas Rosenwald, Louis M Staudt, Elias Campo, Lisa M Rimsza
Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker-the proliferation signature-using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies. Methods Forty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard...
March 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Xin Wang, Lalit Sehgal, Neeraj Jain, Tamer Khashab, Rohit Mathur, Felipe Samaniego
BACKGROUND: Mantle cell lymphoma (MCL) is considered an aggressive subtype of non-Hodgkin's lymphoma with variable treatment responses. There is an urgent need to identify novel markers with prognostic and therapeutic value for MCL. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancers, including MCL. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a lncRNA located at pathognomonic translocation site of t (11; 14) of MCL. MALAT1 is known to be overexpressed in solid tumors and hematologic malignancies...
December 20, 2016: Journal of Translational Medicine
Matthieu Hanf, David Chiron, Sophie de Visme, Cyrille Touzeau, Hervé Maisonneuve, Henry Jardel, Catherine Pellat-Deceunynck, Martine Amiot, Steven le Gouill
BACKGROUND: Mantle Cell Lymphoma (MCL) is often associated with progression, temporary response to therapy and a high relapse rate over time resulting in a poor long-term prognosis. Because MCL is classified as an incurable disease, therapeutic resistance is of great interest. However, knowledge about the biological mechanisms underlying resistance associated with MCL therapies and about associated predictors remains poor. The REFRACT-LYMA Cohort, a multicenter prospective cohort of patients with MCL, is set up to address this limitation...
October 14, 2016: BMC Cancer
Mathieu Gallo, Valère Cacheux, Laure Vincent, Caroline Bret, Ariane Tempier, Caroline Guittard, Alexandra Macé, Nicolas Leventoux, Valérie Costes, Vanessa Szablewski
Leukemic non-nodal mantle cell lymphoma (lMCL) is a particular subtype of mantle cell lymphoma (MCL), characterized by leukemic non-nodal disease and slow progression. Recognition of this entity is relevant to avoid overtreatment. Despite indolent clinical behaviour, lMCL might transform to a more aggressive disease. The purpose of this study was to compare lMCL with classical MCL (cMCL) and aggressive MCL (aMCL) using immunohistochemistry, interphase fluorescence in situ hybridization (FISH), and array-based comparative genomic hybridization, in order to identify biomarkers for lMCL diagnosis and prognosis...
December 2016: Virchows Archiv: An International Journal of Pathology
Qingshan Yang, Lisa S Chen, Min Jin Ha, Kim-Anh Do, Sattva S Neelapu, Varsha Gandhi
PURPOSE: PI3K is a critical node in the B-cell receptor pathway, which is responsible for survival and proliferation of B-cell malignancies. Idelalisib, a PI3Kδ-isoform-specific inhibitor, has been approved to treat B-cell malignancies. Although biological activity of the drug has been evaluated, molecular mechanisms and signaling pathway disruption leading to the biological effects of idelalisib are not yet well defined. Prior laboratory reports have identified transcription and translation as the primary events for attenuation of PI3Kα isoform...
January 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Agata M Bogusz, Adam Bagg
Small B-cell lymphomas and leukemias (SBCLs) are a clinically, morphologically, immunophenotypically and genetically heterogeneous group of clonal lymphoid neoplasms, including entities such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL) and hairy cell leukemia (HCL). The pathogenesis of some of these lymphoid malignancies is characterized by distinct translocations, for example t(11;14) in the majority of cases of MCL and t(14;18) in most cases of FL, whereas other entities are associated with a variety of recurrent but nonspecific numeric chromosomal abnormalities, as exemplified by del(13q14), del(11q22), and +12 in CLL, and yet others such as LPL and HCL that lack recurrent or specific cytogenetic aberrations...
September 2016: Leukemia & Lymphoma
Arati A Inamdar, Andre Goy, Nehad M Ayoub, Christen Attia, Lucia Oton, Varun Taruvai, Mark Costales, Yu-Ting Lin, Andrew Pecora, K Stephen Suh
Despite advances in the development of clinical agents for treating Mantle Cell Lymphoma (MCL), treatment of MCL remains a challenge due to complexity and frequent relapse associated with MCL. The incorporation of conventional and novel diagnostic approaches such as genomic sequencing have helped improve understanding of the pathogenesis of MCL, and have led to development of specific agents targeting signaling pathways that have recently been shown to be involved in MCL. In this review, we first provide a general overview of MCL and then discuss about the role of biomarkers in the pathogenesis, diagnosis, prognosis, and treatment for MCL...
July 26, 2016: Oncotarget
Robert Chen, James Sanchez, Steven T Rosen
Mantle cell lymphoma is an aggressive B-cell non-Hodgkin lymphoma that is often considered incurable. Different clinical and biological biomarkers can be utilized to categorize this lymphoma into various risk levels. Several randomized trials reported in 2015 shed light on the optimal induction therapy. Recent advances include: (1) identification of new pathways to target, (2) novel therapeutics to treat patients with relapsed/refractory disease, and (3) monitoring of minimal residual disease and adoption of a maintenance therapy approach to prevent relapses post induction or post stem cell transplantation...
April 2016: Oncology (Williston Park, NY)
Jia Ruan, Peter Martin
Mantle cell lymphoma (MCL) is a heterogeneous disease, and it has been well-established over the last decade that a subset of patients can have indolent presentation. It is therefore important to adopt a risk-stratified approach in order to minimize unnecessary toxicities while maximizing survival and quality of life in selected MCL patients. This review provides an up-to-date assessment of clinical and pathologic entities associated with indolent disease course and delineates available biomarkers with predictive significance...
June 2016: Current Hematologic Malignancy Reports
Alejandro Roisman, Fuad Huamán Garaicoa, Fernanda Metrebian, Marina Narbaitz, Dana Kohan, Hernán García Rivello, Isolda Fernandez, Astrid Pavlovsky, Miguel Pavlovsky, Luis Hernández, Irma Slavutsky
Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL...
2016: Genes, Chromosomes & Cancer
Roshni Narurkar, Mohammad Alkayem, Delong Liu
Cyclin D1 (CCND1) protein overexpression and/or the t(11;14)(q13;q32) translocation are the pathognomonic hallmarks of mantle cell lymphoma (MCL). However, there have been cases that lacked both t(11;14) and cyclin D1 protein but still had a gene expression profile suggesting a diagnosis of MCL. SOX11 expression was detected in most cyclin D1- negative MCL and can serve as a specific biomarker for the diagnosis of this subset of MCL. Lack of SOX11 expression in MCL was associated with an indolent subset and favorable prognosis...
2016: Biomarker Research
Sachin Diwadkar, Aarti A Patel, Michael G Fradley
Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement...
2016: Case Reports in Cardiology
Martin Dreyling, Simone Ferrero
Based on the profound biological insights of the last years into the molecular pathogenesis of mantle cell lymphoma and the clinical introduction of new targeted drugs, with high efficacy and a good safety profile, the therapeutic scenario for this tumor has been shown to be thoroughly favourable. No longer characterized by a uniformly dismal prognosis, mantle cell lymphoma has been revealed as a spectrum of different diseases, ranging from very indolent cases to highly aggressive and refractory ones. Thus, there is an urgent need to adapt therapy to accommodate the diverse presentations of the disease...
February 2016: Haematologica
Layal El Halabi, David Ghez, Vincent Ribrag
Major advances have significantly improved the outcome of mantle cell lymphoma (MCL). Incorporation of rituximab to CHOP regimen, the adoption of high dose cytarabine with frontline autologous stem cell transplantation in young patients, maintenance rituximab or bortezomib based chemotherapy in elderly patients, improved the disease outcome. Bortezomib, lenalidomide, temsirolimus and ibrutinib have proven their efficacy and are approved for the use in refractory or relapsed MCL patients. Several other molecules are currently being evaluated such as cyclin dependent kinase 4/6 (CDK4/6), phosphoinositide 3-kinase (PI3K), B cell lymphoma-2 (BCL2) and Poly ADP-ribose polymerase (PARP) inhibitors...
March 2016: Expert Review of Hematology
Lei Cao, Lei Fan, Wei Xu, Jian-Yong Li
Mouse double minute 4 (MDM4) as a member of MDM family, is an oncogene emerging as an imperative negative regulator of p53. Tumor suppressor protein p53 plays a crucial role in cell cycle arrest, apoptosis and homeostasis. It has been reported that frequent inactivation of p53 was observed in numerous human cancers including hematologic malignancies. MDM4, the newly discovered modulator of p53 protein, is frequently amplified in various solid tumors such as cutaneous melanoma, retinoblastoma and hematological malignances such as chronic lymphocytic leukemia, acute myeloid leukemia and mantle cell lymphoma...
2015: Current Cancer Drug Targets
Lei Fan, Yi Miao, Yu-Jie Wu, Yan Wang, Rui Guo, Li Wang, An-Li Shen, Yao-Yu Chen, Wei Xu, Jian-Yong Li
Different combinations of biomarkers analyzed by flow cytometry are critical for the accurate diagnosis of leukemic B-cell chronic lymphoproliferative disorders (B-CLPDs). We investigated CD200 and CD148 expression patterns of blood or bone marrow from 374 cases of B-CLPD by multicolor flow cytometry. Our results showed that CD200 and CD148 expression patterns distinguished different types of B-CLPD. CD200 mean fluorescence intensity (MFI) or CD148 MFI had a high sensitivity and specificity to differentiate mantle cell lymphoma (MCL) from chronic lymphocytic leukemia (CLL)...
2015: Leukemia & Lymphoma
Changhoon Yoo, Dok Hyun Yoon, Shin Kim, Jooryung Huh, Chan-Sik Park, Chan-Jeong Park, Sang-Wook Lee, Cheolwon Suh
Although serum beta-2 microglobulin (B2M) has been suggested as a prognostic factor for mantle cell lymphoma (MCL), additional data are necessary to confirm its role. Between November 2005 and July 2014, a total of 52 patients with MCL were identified from the database of Asan Medical Center, Seoul, Korea. Pretreatment serum B2M information was available in 50 patients (96%). Overall survival (OS) was compared according to the serum B2M level with a cut-off value of 2.5 mg/L. The median MCL international prognostic index (MIPI) score was 5...
March 2016: Hematological Oncology
Martin Dreyling, Simone Ferrero, Niklas Vogt, Wolfram Klapper
The elucidation of crucial biologic pathways of cell survival and proliferation has led to the development of highly effective drugs, some of which have markedly improved mantle cell lymphoma (MCL) therapeutic opportunities in the past 10 years. Moreover, an undeniable clinical heterogeneity in treatment response and disease behavior has become apparent in this neoplasm. Thus, the need for biologic markers stratifying patients with MCL in risk classes deserving different treatment approaches has recently been fervently expressed...
October 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Etienne Mahe, Ariz Akhter, Anne Le, Lelsey Street, Payam Pournaziri, Farid Kosari, Meer-Taher Shabani-Rad, Douglas Stewart, Adnan Mansoor
Mantle cell lymphoma (MCL) is an aggressive disease with poor overall survival, attributable in part to frequent defects of the DNA repair genes. In such malignancies, additional inhibition of the ubiquitous DNA damage repair protein, poly-ADP ribose polymerase-1 (PARP1) has shown enhanced cytotoxicity (so-called synthetic lethality). We studied PARP1 expression in a series of clinical cases of MCL, with the secondary aim to ascertain the relationship between PARP1 expression and DNA repair gene expression (namely ATM and p53) by immunohistochemical methods...
December 2015: Hematological Oncology
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