The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The disease's complexity is underpinned by a variety of genetic and molecular abnormalities that drive its progression.

Methods: This review was conducted through a state-of-The-art literature search, primarily utilizing PubMed to gather peer-reviewed articles.

FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk.

Etiological links to multiple myeloma (MM) remain poorly understood, though emerging evidence suggests a significant hereditary component. This review integrates current literature on inherited factors contributing to MM risk, synthesizing both epidemiologic and genomic data. We examine familial clustering patterns, assess genome-wide association studies (GWAS) that reveal common genetic variants linked to MM, and explore rare, high-penetrance variants in key susceptibility genes.

Mechanosensitive nuclear uptake of chemotherapy.

The nucleus is at the nexus of mechanotransduction and the final barrier for most first line chemotherapeutics. Here, we study the intersection between nuclear-cytoskeletal coupling and chemotherapy nuclear internalization. We find that chronic and acute modulation of intracellular filaments changes nuclear influx of doxorubicin (DOX).

Protein-Specific Crowding Accelerates Aging in Protein Condensates.

Macromolecular crowding agents, such as poly(ethylene glycol) (PEG), are often used to mimic cellular cytoplasm in protein assembly studies. Despite the perception that crowding agents have an inert nature, we demonstrate and quantitatively explore the diverse effects of PEG on the phase separation and maturation of protein condensates. We use two model proteins, the FG domain of Nup98 and bovine serum albumin (BSA), which represent an intrinsically disordered protein and a protein with a well-established secondary structure, respectively.

Interaction-Dependent Secondary Structure of Peptides in Biomolecular Condensates.

Biomolecular condensates provide a mechanism for compartmentalization of biomolecules in eukaryotic cells. These liquid-like condensates are formed via liquid-liquid phase separation, by a plethora of interactions, and can mediate several biological processes in healthy cells. Expansions of dipeptide repeat proteins, DPRs, in which arginine rich DPRs like poly-proline-arginine (PR), and poly-glycine-arginine (GR), partition RNA into condensates can however induce cell toxicity.