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

## TL;DR

This case report uses whole genome and single-cell RNA sequencing to study the clonal evolution and heterogeneity in a rare aggressive form of multiple myeloma called secondary plasma cell leukemia.

## Contribution

The study provides new insights into genomic instability and clonal evolution in secondary plasma cell leukemia through combined sequencing approaches.

## Key findings

- A major clone with a monoallelic TP53 mutation was identified in the initial stage of the disease.
- A subclone with a biallelic TP53 mutation and increased 1q21 copy number emerged during progression.
- Single-cell RNA sequencing revealed a PCL population with high CKS1B expression.

## Abstract

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 TP53 mutation. During progression, a subclone with a biallelic TP53 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.

Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.