Primary Plasma Cell Leukemia Displaying t(11;14) have specific genomic, transcriptional and clinical feature

Primary plasma cell leukemia is an aggressive form of multiple myeloma (MM) that has not benefited from recent therapeutic advances in the field. Because very rare and heterogeneous, it remains poorly understood at the molecular level. To address this issue, we performed DNA and RNA sequencing of sorted plasma cells form a large cohort of 90 newly diagnosed pPCL, and compared to MM. We observed that pPCL present a specific genomic landscape with a high prevalence of t(11;14) (about half) and high-risk genomic features such as del(17p), gain 1q, del1p32. In addition, pPCL display a specific transcriptome when compared to MM. We then aimed at specifically characterize pPCL with t(11;14). We observed that this sub entity displayed significantly more TP53 mutations but less adverse cytogenetic abnormalities. This translated in better overall survival when compared to pPCL without t(11.14) (39.2 months vs 17.9 months, p=0.002). Finally, pPCL with t(11;14) displayed a specific transcriptome, including differential expression of BCL2 family members. This study is the largest series of patients with pPCL reported so far