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

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Plasma cell leukemia (PCL) is a rare and aggressive hematologic malignancy.
• Understanding the genetic landscape of PCL is crucial for developing targeted therapies.

Purpose of the Study:

• To compare the genetic profiles of plasma cell leukemia (PCL) with multiple myeloma (MM) using next-generation sequencing (NGS).
• To identify potential therapeutic targets in PCL based on genetic aberrations.

Main Methods:

• Next-generation sequencing (NGS) was performed on plasma cells from 18 PCL patients (peripheral blood and bone marrow).
• NGS data were compared with 1742 multiple myeloma (MM) samples.
• Analysis focused on mutations and translocations in key genes.

Main Results:

• TP53, CCND1, and KRAS mutations were common in both PCL and MM.
• PCL showed significantly higher frequencies of alterations in DIS3, CCND2, PIK3R1, and MAP3K1 compared to MM.
• Translocations, including IGH::CCND1 and IGH::MYC, were more frequent in PCL, with IGH::MYC reaching statistical significance.

Conclusions:

• PCL harbors distinct genetic aberrations compared to MM, particularly in DIS3, CCND2, PIK3R1, MAP3K1, and IGH::MYC.
• Druggable targets such as BRAF, CCND1, PIK3R1, and RAS alterations present opportunities for biomarker-driven clinical trials in PCL.