Plasma Cell Leukemia: Genomic Features and Their Potential Relevance for Exploring Clinical Actionability Open Access

• Sequencing PB and BM in patients with PCL is feasible. Mutations in TP53, KRAS, and NRAS, and translocations involving CCND1 were common

• CCND1, RAS, BRAF, and PIK3R1 alterations merit study for clinical actionability.

Plasma cell leukemia (PCL) is rare and aggressive. Plasma cells from PCL patients were interrogated by next-generation sequencing (NGS). We compared NGS in 18 PCL patients (peripheral blood, n = 10; bone marrow [BM], n = 8) and 1,742 multiple myeloma (MM) samples. Mutations of TP53, CCND1, and KRAS were commonly seen in both diseases. Alterations in DIS3 (17% vs. 1%), CCND2 (22% vs. 15%), PIK3R1 (6% vs. 0%), and MAP3K1 (6% vs. 2%) were more common in PCL compared to MM (p < 0.05). Translocations occurred in 11 (61.1%) PCL patients; IGH::CCND1 and IGH::MYC were more frequent in PCL compared to MM (22% vs. 14%, p = NS, and 11% vs. 1%, p < 0.05). Druggable aberrations in BRAF, CCND1, PIK3R1, and RAS may be targeted in biomarker-driven therapeutic clinical trials.