Plasma cell leukemia: genomic features and their potential relevance for exploring clinical actionability

Plasma cell leukemia (PCL) is rare and aggressive. Plasma cells from patients with PCL were examined using next-generation sequencing (NGS). We compared NGS data from 18 patients with PCL (peripheral blood, n = 10; bone marrow, n = 8) and 1742 multiple myeloma (MM) samples. Mutations of TP53, CCND1, and KRAS were commonly observed 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 than in MM (P< .05). Translocations occurred in 11 (61.1%) patients with PCL; IGH::CCND1 and IGH::MYC were more frequent in PCL than in MM (22% vs 14%, P = not significant and 11% vs 1%, P< .05, respectively). Druggable aberrations in BRAF, CCND1, PIK3R1, and RAS may be targeted in biomarker-driven therapeutic clinical trials.