Whole Genome and Single‐Cell RNA Sequencing Reveals Clonal Evolution and Heterogeneity of Secondary Plasma Cell Leukemia: A Case Report

Secondary plasma cell leukemia (sPCL) is a rare, aggressive manifestation of multiple myeloma (MM). We report a 75-year-old Japanese man with anemia as the chief complaint and IgG-λ MM that rapidly progressed to sPCL. Whole genome sequencing using Canopy revealed a major clone with a monoallelic <i>TP53</i> mutation. During progression, a subclone with a biallelic <i>TP53</i> mutation expanded, and the 1q21 copy number increased. Single-cell RNA-sequencing identified an emergent PCL population with high CKS1B expression. These data demonstrate genomic instability and clonal evolution during sPCL development, underscoring the need for approaches accounting for tumor heterogeneity in MM. <b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission.