Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.

Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.

Multi-Cohort High-Dimensional Proteomics Reveals Early Risk Markers for Lymphoid Cancer Subtypes.

This study aims to investigate the early stages of lymphoid malignancy pathogenesis and identify novel pre-diagnostic proteomic markers for lymphoma. Using the SomaScan-7K platform, we analyzed 6,412 unique plasma proteins in a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, comprising 4,565 participants (484 incident lymphoid malignancy cases, median follow-up 9 years). We identified over 500 unique protein-lymphoid malignancy associations.

Phenome-to-genome insights for evaluating root system architecture in field studies of maize.

Understanding the genetic basis of root system architecture (RSA) in crops requires innovative approaches that enable both high-throughput and precise phenotyping in field conditions. In this study, we evaluated multiple phenotyping and analytical frameworks for quantifying RSA in mature, field-grown maize in three field experiments. We used forward and reverse genetic approaches to evaluate >1700 maize root crowns, including a diversity panel, a biparental mapping population, and maize mutant and wild-type alleles at two known RSA genes, DEEPER ROOTING 1 (DRO1) and Rootless1 (Rt1).

Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15).

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival.

Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy.