Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors.

Primary central nervous system lymphoma (PCNSL) is clinically challenging due to its location and small biopsy size, leading to a lack of comprehensive molecular and biologic description. We previously demonstrated that 91% of PCNSL belong to the activated B-cell-like (ABC) molecular subtype of diffuse large B-cell lymphoma (DLBCL). Here we investigated the expression of 739 cancer related genes in HIV (-) patients using NanoString digital gene expression profiling in 25 ABC-PCNSL and 43 ABC-systemic DLBCL, all tumors were EBV (-).

Malignancy-associated HLH: mechanisms, diagnosis, and treatment of a severe hyperinflammatory syndrome.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by uncontrolled immune activation. While traditionally associated with genetic mutations affecting cytotoxic function, recent advances have highlighted the prevalence and significance of HLH in adults, particularly in hematologic malignancies. This review focuses on malignancy-associated HLH (M-HLH), a complex and challenging condition with a poor prognosis.

Comparison of Survivorship Care Guidelines for Patients With Lymphoma: Recommendations for Harmonization and Future Research Agenda.

Purpose: Lymphomas are a heterogeneous group of diseases that develop in individuals of all ages and have variable prognoses. Improved survival resulting from therapy advances has led to the emergence of diverse late effects. Although several (US)-based organizations have developed survivorship guidelines, the distinct features of lymphoma subtypes and diverse therapies used raise concerns regarding their applicability to lymphoma survivors.

Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance.

Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL.

Blood Plasma Methylated DNA Markers in the Detection of Lymphoma: Discovery, Validation, and Clinical Pilot.

Lymphoma is one of the leading causes of cancer and cancer deaths and yet has not been amenable to population screening. The role of methylated DNA markers (MDMs) in the detection of lymphoma has not been extensively studied. We aimed to discover, validate, and test tissue-derived MDMs of lymphoma in archival plasma specimens.

Characteristics and outcomes of incidentally diagnosed diffuse large B-cell lymphoma and implications for cancer screening.

Differences in characteristics and outcomes between incidental and symptomatic presentations of Large B-Cell Lymphoma.

DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration.

Real-world impact of differences in the WHO and ICC classifications of non-Hodgkin lymphoma: a LEO cohort study analysis.

Recent introduction of 2 different lymphoma classifications has raised concerns about consistency in diagnosis, management, and clinical trial enrollment. Data from a large cohort reflecting real-world clinical practice suggest that differences between the classifications will affect <1% of non-Hodgkin lymphomas.

Risk of Incident Melanoma Among Individuals With Low-Count Monoclonal B-Cell Lymphocytosis.

Purpose: Chronic lymphocytic leukemia (CLL)-phenotype monoclonal B-cell lymphocytosis (MBL) is a premalignant condition that is roughly 500-fold more common than CLL. It is unknown whether the two-fold increased risk of developing melanoma associated with CLL extends to individuals with MBL.

Methods: Using the Mayo Clinic Biobank, we identified participants who were 40 years or older with no previous hematological malignancies, who resided in the 27 counties around Mayo Clinic, and who had available biospecimens for screening.

Utility of Targeted Sequencing Compared to FISH for Detection of Chronic Lymphocytic Leukemia Copy Number Alterations.

Chronic lymphocytic leukemia (CLL) is characterized by multiple copy number alterations (CNAs) and somatic mutations that are central to disease prognosis, risk stratification, and mechanisms of therapy resistance. Fluorescence in situ hybridization (FISH) panels are widely used in clinical applications as the gold standard for screening prognostic chromosomal abnormalities in CLL. DNA sequencing is an alternative approach to identifying CNAs but is not an established method for clinical CNA screening.

Stratifying heart failure patients with graph neural network and transformer using Electronic Health Records to optimize drug response prediction.

Objectives: Heart failure (HF) impacts millions of patients worldwide, yet the variability in treatment responses remains a major challenge for healthcare professionals. The current treatment strategies, largely derived from population based evidence, often fail to consider the unique characteristics of individual patients, resulting in suboptimal outcomes. This study aims to develop computational models that are patient-specific in predicting treatment outcomes, by utilizing a large Electronic Health Records (EHR) database.

Assessing and attenuating the impact of selection bias on spatial cluster detection studies.

Spatial cluster analyses are commonly used in epidemiologic studies of case-control data to detect whether certain areas in a study region have an excess of disease risk. Case-control studies are susceptible to potential biases including selection bias, which can result from non-participation of eligible subjects in the study. However, there has been no systematic evaluation of the effects of non-participation on the findings of spatial cluster analyses.

Synoptic Reporting by Summarizing Cancer Pathology Reports using Large Language Models.

Background: Synoptic reporting, the documenting of clinical information in a structured manner, is known to improve patient care by reducing errors, increasing readability, interoperability, and report completeness. Despite its advantages, manually synthesizing synoptic reports from narrative reports is expensive and error prone when the number of structured fields are many. While the recent revolutionary developments in Large Language Models (LLMs) have significantly advanced natural language processing, their potential for innovations in medicine is yet to be fully evaluated.

Defining primary refractory large B-cell lymphoma.

Patients with large B-cell lymphoma (LBCL) that fail to achieve a complete response (CR) or who relapse early after anthracycline-containing immunochemotherapy (IC) have a poor prognosis and are commonly considered to have "primary refractory disease." However, different definitions of primary refractory disease are used in the literature and clinical practice. In this study, we examined variation in the time to relapse used to define refractory status and association with survival outcomes in patients with primary refractory LBCL in a single-center prospective cohort with validation in an independent multicenter cohort.

Low-frequency and rare genetic variants associated with rheumatoid arthritis risk.

Rheumatoid arthritis (RA) has an estimated heritability of nearly 50%, which is particularly high in seropositive RA. HLA alleles account for a large proportion of this heritability, in addition to many common single-nucleotide polymorphisms with smaller individual effects. Low-frequency and rare variants, such as those captured by next-generation sequencing, can also have a large role in heritability in some individuals.