Genomic characterization of clonal B-cell lymphocytosis of marginal zone origin with MYC rearrangements.

Monoclonal B-cell lymphocytosis of marginal zone origin (MBL-MZ) is an indolent clonal disorder with potential progression to lymphoma. MYC rearrangements (MYCr), typically linked to aggressive B-cell lymphomas, have not been reported in MBL-MZ. We describe three MBL-MZ cases with MYCr and TP53 alterations, detected via karyotyping, FISH, and optical genome mapping. We genetically characterized these cases by NGS using a custom panel including 31 MZ-related genes, and we assessed MYC expression via RNA-Seq. Despite harboring these high-risk alterations, all cases exhibited stable clinical courses without lymphoma transformation. These findings suggest MYCr alone may not drive aggressive behavior in MBL-MZ, underscoring the need for integrated genetic and clinical assessment to prevent overtreatment.