microRNA sequencing for biomarker detection in the diagnosis, classification and prognosis of Diffuse Large B Cell Lymphoma.

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.

Pure white cell aplasia an exceptional condition in the immunological conundrum of thymomas: Responses to immunosuppression and literature review.

Thymomas are tumours frequently associated with autoimmune manifestations or immunodeficiencies like Good syndrome. In rare cases, pure white cells aplasia (PWCA) has been described in association with thymomas. PWCA is characterized by agranulocytosis of autoimmune background primary refractory to granulocyte colony-stimulating factor (G-CSF). It is necessary the use of immunosuppressor to allow granulocyte recovery. Without treatment, it could be fatal.

Single versus tandem autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma and high-risk cytogenetics. A retrospective, open-label study of the PETHEMA/Spanish Myeloma Group (GEM).

Tandem ASCT has been suggested as a valid approach to improve the prognosis of patients with MM and HR cytogenetic. In this observational, retrospective study, 213 patients with newly diagnosed MM and HR cytogenetic in 35 hospitals from the Spanish Myeloma Group underwent single or tandem ASCT between January 2015 and December 2019 after induction with VTD/VRD. HR cytogenetic was defined as having ≥1 of the following: del17p, t(4;14), t(14;16) or gain 1q21. More patients in the tandem group had R-ISS 3 and >1 cytogenetic abnormality at diagnosis. With a median follow-up of 31 months (range, 10-82), PFS after single ASCT was 41 months versus 48 months with tandem ASCT (p = 0.33). PFS in patients with del17p undergoing single ASCT was 41 months, while 52% of patients undergoing tandem ASCT were alive and disease free at 48 months. In conclusion, tandem ASCT partly overcomes the bad prognosis of HR cytogenetic.

Systematic review of the potential of MicroRNAs in the management of patients with follicular lymphoma.

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: miR-155-5p 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 diagnosed during first trimester of pregnancy with excellent outcome after plasma exchange and rituximab, a case report.

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.

Prognostic and therapeutic value of somatic mutations 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.

Cell-free DNA as a biomarker in diffuse large B-cell lymphoma: A systematic review.

Cell-free DNA (cfDNA), which is DNA released from cells into the circulation, is one of the most promising non-invasive biomarkers in cancer. This approach could be of interest for the management of Diffuse Large B-Cell Lymphoma (DLBCL) patients, which is the most common non-Hodgkin lymphoma. Then, the aim of this systematic review was to define the utility of cfDNA in this disease. Selected articles were classified in four groups, depending on the aspects of cfDNA studied, i.e. concentration, methylation, IgH gene rearrangements, and somatic mutations. While concentration and methylation of cfDNA need to be further analyzed, IgH gene rearrangements and somatic mutations seem to be the most promising biomarkers to date. Their detection has been shown to allow disease monitoring and early prediction of relapse. Although more efforts and standardization of techniques are needed, studying cfDNA in liquid biopsy may help improve the outcome of DLBCL patients.

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

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy, with highly variable outcomes among patients. Although classification and prognostic tools have been developed, standard therapy still fails in 30-40% of patients. Hence, identification of novel biomarkers is needed. Recently, circulating microRNAs (miRNAs) have been suggested as non-invasive biomarkers in cancer. Our aim was to review the potential role of circulating miRNAs as biomarkers for diagnosis, classification, prognosis, and treatment response in DLBCL. We performed a search in PubMed using the terms [(('Non-coding RNA') OR ('microRNA' OR 'miRNA' OR 'miR') OR ('exosome') OR ('extracellular vesicle') OR ('secretome')) AND ('Diffuse large B cell lymphoma' OR 'DLBCL')] to identify articles that evaluated the impact of circulating miRNAs as diagnosis, subtype, treatment response or prognosis biomarkers in DLBCL in human population. Among the twelve articles that met the inclusion criteria, eleven considered circulating miRNAs as biomarkers for diagnosis, two for classification, and five for prognosis or treatment response. The limited number of studies performed and lack of consistency in results make it difficult to draw conclusions about the role of circulating miRNAs as non-invasive biomarkers in DLBCL. Although the preliminary associations observed seem promising, the only consistent result is the upregulation of mir-21 in DLBCL patients, which could be a biomarker for diagnosis. Further studies are needed.