Circulating miRNAs as biomarkers in diffuse large B-cell lymphoma: a systematic review Circulating miRNAs as biomarkers in diffuse large B-cell Lymphoma: a systematic review

Diffuse large B-cell lymphoma (DLBCL), the most common type of Non-Hodgkin lymphoma (NHL), is a highly heterogeneous and aggressive disease. Regardless of this heterogeneity, all patients receive the same first-line therapy, which fails in 30-40 % of patients, who are either refractory or relapse after remission. With the aim of stratifying patients to improve treatment outcome, different clinical and genetic biomarkers have been studied. The present systematic review aimed to identify somatic mutations that could serve as prognosis biomarkers or as therapeutic target mutations in DLBCL. Regarding their role as prognostic markers, mutations in CD58 and TP53 seem the most promising predictors of poor outcome although the combination of different alterations and other prognostic factors could be a more powerful strategy. On the other hand, different approaches regarding targeted therapy have been proposed. Therefore, mutational analysis could help guide treatment choice in DLBCL yet further studies and clinical trials are needed.

Despite being considered a single disease, Diffuse Large B Cell Lymphoma (DLBCL) presents with variable backgrounds, which results in heterogeneous outcomes among patients, with 40% of them still having primary refractory disease or relapse. Thus, novel biomarkers are needed. In addition, multiple factors regarding its pathogenesis remain unclear. In this context, recent investigations point to the relevance of microRNAs (miRNAs) in cancer. However, regarding DLBCL, there is inconsistency in the data reported. Therefore, in this work, the main goals were to determine a miRNA set with utility as biomarkers for DLBCL diagnosis, classification, prognosis and treatment response, as well as to decipher the mechanism of action of deregulated miRNAs in the origin of the disease. We analyzed miRNA expression in a cohort of 78 DLBCL patients and 17 controls using small RNA sequencing and performed a miRNA-mRNA interaction network analysis. This way, we were able to define new miRNA expression signatures for diagnosis, classification, treatment response and prognosis, and we identified plausible mechanisms of action by which deregulated miRNAs could be involved in DLBCL pathogenesis. In summary, our study remarks that miRNAs could play an important role in DLBCL.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma and usually presents as an indolent disease. However, some patients present poor outcomes, and FL can transform into more aggressive lymphomas, such as Diffuse Large B cell lymphoma (DLBCL). MicroRNAs (miRNA) are small RNA molecules that participate in posttranscriptional regulation of gene expression, that are emerging biomarkers in cancer. In this systematic review, we included studies evaluating miRNA expression in tumor tissue as diagnosis, transformation or prognosis biomarkers in FL. We identified several miRNAs, which could be diagnostic biomarkers in FL: miR155-5p and miR-9-3p as miRNAs of potential utility for diagnosis of FL, and miR-150 and miR-17-92 cluster for differential diagnosis between FL and DLBCL. Prognosis and transformation prediction have not been studied in enough depth to draw solid conclusions. Further research is needed to exploit the potential of this field.

Acquired thrombotic thrombocytopenic purpura is a life‐threatening condition that rarely presents during pregnancy. Early diagnosis and treatment with plasma exchange is needed to achieve a good pregnancy outcome.