Whole Transcriptome Sequencing Reveals Cancer-Related, Prognostically Significant Transcripts and Tumor-Infiltrating Immunocytes in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) subtype characterized by overexpression of CCND1 and SOX11 genes. It is generally associated with clinically poor outcomes despite recent improvements in therapeutic approaches. The genes associated with the development and prognosis of MCL are still largely unknown. Through whole transcriptome sequencing (WTS), we identified mRNAs, lncRNAs, and alternative transcripts differentially expressed in MCL cases compared with reactive tonsil B-cell subsets. CCND1, VCAM1, and VWF mRNAs, as well as MIR100HG and ROR1-AS1 lncRNAs, were among the top 10 most significantly overexpressed, oncogenesis-related transcripts. Survival analyses with each of the top upregulated transcripts showed that MCL cases with high expression of VWF mRNA and low expression of FTX lncRNA were associated with poor overall survival. Similarly, high expression of MSTRG.153013.3, an overexpressed alternative transcript, was associated with shortened MCL survival. Known tumor suppressor candidates (e.g., PI3KIP1, UBXN) were significantly downregulated in MCL cases. Top differentially expressed protein-coding genes were enriched in signaling pathways related to invasion and metastasis. Survival analyses based on the abundance of tumor-infiltrating immunocytes estimated with CIBERSORTx showed that high ratios of CD8+ T-cells or resting NK cells and low ratios of eosinophils are associated with poor overall survival in diagnostic MCL cases. Integrative analysis of tumor-infiltrating CD8+ T-cell abundance and overexpressed oncogene candidates showed that MCL cases with high ratio CD8+ T-cells and low expression of FTX or PCA3 can potentially predict high-risk MCL patients. WTS results were cross-validated with qRT-PCR of selected transcripts as well as linear correlation analyses. In conclusion, expression levels of oncogenesis-associated transcripts and/or the ratios of microenvironmental immunocytes in MCL tumors may be used to improve prognostication, thereby leading to better patient management and outcomes.

Spontaneous remission of chronic lymphocytic leucemia in a patient with SARS-CoV2.

Although novel therapies have improved the treatment outcome of patients, chronic lymphocytic leukaemia (CLL) is still considered incurable. Recently, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), causing coronavirus disease 2019 (Covid 19), emerged in late 2019, and it has posed a global health threat. In a limited number of cases, it has been shown that some lymphoma types spontaneously regress after SARS-CoV2 infection suggesting that the infection can trigger de immune system against the tumour cell. Cross-reactivity of pathogen-specific T cells with tumour antigens and natural killer cell activation can be the possible mechanism of this hypothesis.

Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosis.

Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.

Unexpected hematologic malignancies after prostatectomy: Case report and literature review.

INTRODUCTION: Voiding symptoms, storage symptoms and post-voiding symptoms together constitute lower urinary tract symptoms (LUTS). Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The most common finding is lymphadenomegaly. Although infrequent, extranodal sites of involvement such as prostate can be detected. Mantle cell lymphoma (MCL) is a subtype of B cell non-Hodgkin lymphomas. Extranodal involvement findings such as prostate may be observed. In this case report, we will present a case in which we performed an open suprapubic prostatectomy (Freyer's) and had CLL as a result of pathology, and a case whose pathology was MCL after transurethral resection of the prostate. CASE 1: A 60-year-old male patient with LUTS for 6 years. Open suprapubic prostatectomy (Freyer's) was performed on the patient. The pathology result of the prostatectomy material was compatible with CLL involvement. CASE 2: A 62-year-old male patient with LUTS for 4 years. Transurethral resection of the prostate (TUR-P) was performed on the patient. The pathology result of the prostate was compatible with MCL involvement. DISCUSSION AND CONCLUSION: There are limited number of cases have been reported about CLL pathology after prostatectomy due to benign prostatic obstruction (BPO). There is no study indicating how often CLL pathology is seen after open prostatectomy or TUR-P due to BPO. In patients with CLL pathology after RRP, open prostatectomy, TUR-P, the need for additional surgery, the difference in prognosis or the difference between the treatment have not been shown in the studies. It should be kept in mind that patients with leukocytosis, lymphocytosis, cytopenias, and LUTS in their clinical presentation and who have not yet been diagnosed with CLL and other hematological malignancies such as mantle cell lymphoma may also have prostate gland involvement and can be diagnosed incidentally by any prostatic intervention.

Can Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio at Day +100 be used as a prognostic marker in Multiple Myeloma patients with autologous transplantation?

BACKGROUND: Recent reports have showed that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are predictors of progression-free survival (PFS) and overall survival (OS) in many types of cancer. This study evaluates the predictive value of NLR, MLR, and PLR for survival in MM patients treated with to ASCT. METHODS: A set of data consisting of 150 patients who underwent autologous stem cell transplantation (ASCT) for MM was collected retrospectively. The prognostic value of NLR, MLR, and PLR was investigated with Kaplan-Meier method. RESULTS: The prognostic value of NLR, MLR, and PLR was analyzed by a receiver operating characteristic (ROC) curve established to determine the cutoff. These cutoff values of NLR, PLR, and MLR were found 1.46, 86, and 0.27, respectively, on the 100th day of post-transplantation period. The overall survival (OS) and the post-transplantation OS of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation were shorter than the other group (P = 0.05, P = 0.018 [NLR], P = 0.05, P = 0.002 [MLR], P = 0.000, P = 0.001 [PLR]). The post-transplantation progression-free survival (PFS) of the patients with high NLR, MLR, and PLR levels on the 100th day of post-transplantation was shorter as well (P = 0.036, P = 0.001, P = 0.001, respectively). CONCLUSION: As increased NLR, MLR, and PLR predicted poor clinical outcome in MM patients with autologous transplantation in this study, they may serve as cost-effective and rapidly available prognostic biomarkers for these patients.

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS: The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained. In groups I, II, and III, only saline, KRG, and CDDP, respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP injections were administered on day 11. On day 14, final DPOAEs and ABR measurements were completed. The rats were then sacrificed, and their inner ear structures were evaluated by transmission electron microscopy. RESULTS: In the first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP ototoxicity. This protection was mainly due to a decline in apoptotic gene expression and an increase in antiapoptotic gene expression. In the in vivo part of the study, we found that both KRG doses had otoprotective effects. This protection was more prominent at the lower dose, especially on the spiral ganglion and the brainstem. CONCLUSION: KRG was shown to be an otoprotective agent against CDDP-induced ototoxicity both in vivo and in vitro.

Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity.

OBJECTIVES/HYPOTHESIS: Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem. STUDY DESIGN: In vivo study using an animal model. METHODS: Thirty-two male Wistar albino rats were divided into six groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were made. In groups I, II, and III, only saline, RV, and CDDP were given, respectively. Group IV, V, and VI animals were administered 10 mg/kg/day, 1 mg/kg/day, and 0.1 mg/kg/day of RV for 10 days, respectively, before 16 mg/kg CDDP injections were administered on day 11. All animals were sacrificed after repeated DPOAEs and ABR measurements were made on day 14. Cochleas of animals were investigated with transmission electron microscopy. Apoptosis were investigated with caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in the brainstem. RESULTS: In groups IV and V, DPOAEs and ABR findings revealed that oral administration of RV 10 mg/kg/day and 1 mg/kg/day doses before CDDP injection enhanced ototoxicity. In group VI, electomicroscopy revealed better ultrastructural findings than in the cisplatin group; however, these changes were not reflected in the audiological findings accordingly. CONCLUSIONS: Our results implied that there were noticeable differences between different oral RV doses used for cisplatin ototoxicity. Especially in higher doses, RV was observed to enhance cisplatin ototoxicity.