1,721,186 research outputs found

    Infections and Follicular Lymphoma: Is there a Link?

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    Several infectious agents appear to provide a proliferative signal -- "antigen-drive" - that could be implicated in the pathogenesis of various type of Non-Hodgkin Lymphoma (NHL). A classical model of the infection-driven lymphoproliferative disorder is Helicobacter pylori-induced gastric MALT lymphoma, where antibiotic therapy allows the eradication of both the infectious agent and the clonal B-cell expansion. Following the footsteps of this example, several retrospective studies have found a correlation with other pathogens and B-cell Lymphomas, adding new relevant information about pathogenesis and laying the groundwork for chemotherapy-free treatments. Although no clear association has been found between infectious agents and Follicular Lymphoma (FL), a growing number of biological and clinical observations suggests the interaction of physiological and pathological microbial populations also in this subtype of lymphoma. In the last few years, epidemiological studies investigating the association of known risk factors and FL found a potential correlation with viral or bacterial infections; moreover, recent findings of the stimulation of FL clones support the importance of microbial exposure to lymphomagenesis and disease progression.In the following review we make an attempt to find tangible evidence for a role of either physiological and pathological exogenous microbial species in the pathogenesis of FL, and try to integrate the findings coming from epidemiological, biological and interventional studies to define future novel treatment and prevention strategies for FL

    Minimal Residual Disease in Mantle Cell Lymphoma: Methods and Clinical Significance

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    Several biological and clinical features have been recognized in mantle cell lymphoma (MCL). In recent years, the minimal residual disease (MRD) has been extensively investigated and is now considered as one of the strongest clinical predictors in this lymphoma. This article reviews methods used for the assessment of MRD in MCL and discusses their strengths and weaknesses. In addition, it examines the MRD contribution to the biology knowledge of MCL and the development of effective strategies for its management, including the possibility of personalized treatment based on MRD response

    Droplet digital PCR for minimal residual disease detection in mature lymphoproliferative disorders

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    Minimal residual disease (MRD) detection has a powerful prognostic relevance for response evaluation and prediction of relapse in hematological malignancies. Real-time quantitative PCR (qPCR) has become the settled and standardized method for MRD assessment in lymphoid disorders. However, qPCR is a relative quantification approach, since it requires a reference standard curve. Droplet digitalTM PCR (ddPCRTM) allows a reliable absolute tumor burden quantification withdrawing the need for preparing, for each experiment, a tumor-specific standard curve. We have recently shown that ddPCR has a good concordance with qPCR and could be a feasible and reliable tool for MRD monitoring in mature lymphoproliferative disorders. In this chapter we describe the experimental workflow, from the detection of the clonal molecular marker to the MRD monitoring by ddPCR, in patients affected by multiple myeloma, mantle cell lymphoma and follicular lymphoma. However, standardization programs among different laboratories are needed in order to ensure the reliability and reproducibility of ddPCR-based MRD results

    Minimal Residual Disease in Indolent Lymphomas: A Critical Assessment

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    Indolent non-Hodgkin lymphomas (iNHL) are a heterogeneous group of pathologies characterized by a prolonged natural history and good response to treatment. They also have a tendency to relapse, in some cases with a worse prognosis. One of the main objectives in the newest clinical trials is to identify patients at high risk of relapse. This cannot be accomplished using only clinical prognostic scores. Detection of minimal residual disease (MRD) is effective in evaluating long-term disease response, with a strong and independent predictive value that was demonstrated in large cohorts of patients. Analysis of MRD allows patient stratification based on the risk for relapse; therefore, different therapeutic programs can be designed based on the response characteristics. This tailored therapy is already happening in current clinical trials. Limits imposed by traditional PCR-based tools are being overcome due to new molecular biology techniques like droplet digital PCR and next generation sequencing. Although these techniques are not yet standardized, they will likely increase the reliability and ensure broad applicability of MRD detection in future years

    Controversies in the treatment of follicular lymphoma

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    The overall prognosis of patients with follicular lymphoma has substantially improved over the last decades with a 10-year overall survival of around 80% for the majority of patients. However, for most patients follicular lymphoma it is still a relapsing and remitting disease. Furthermore, certain subsets of patients still have much shorter survival. Currently, there is no established standard how to treat high-risk follicular lymphoma. With advances in the understanding of the biology and pathogenesis of B cell malignancies, a plethora of new compounds have been investigated in FL. These compounds have the potential to increase efficacy if added to current regimens or even replace them. The implementation of these compounds in treatment algorithms is another unsolved issue. This overview highlights major controversies in the treatment of follicular lymphoma and discusses the most recent and relevant clinical trials

    N- and K-ras oncogenes in plasma cell dyscrasias

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    N- and K-ras oncogene mutations represent the most frequent molecular lesions in plasma cell dyscrasias. They are not randomly distributed since they are detectable in multiple myeloma (MM) (9-31%) and plasma cell leukemia (PCL) (30%), and not in monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma (SP). Codons 12, 13 and 61 of N- and K-ras genes have been found mutated. Mutations affecting codon 61 of N-ras gene are the most frequent finding. A heterogeneous pattern of mutations is described with a prevalence of purine-pyrimidine transversions. Ras gene mutations have been predominantly detected in myelomas characterized by an advanced stage disease, and adverse prognostic parameters. These findings suggest that ras mutations represent a late molecular lesion and may be implicated in tumor progression rather than tumor initiation
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