Working Toward a Genomic Prognostic Classification of Waldenstrom Macroglobulinemia C-X-C Chemokine Receptor Type 4 Mutation and Beyond

Waldenstrom macroglobulinemia is a rare indolent B-cell lymphoma. Whole-exome sequencing studies have improved our knowledge of the Waldenstrom macroglobulinemia mutational landscape. The MYD88 L265P mutation is present in nearly 90% of patients with Waldenstrom macroglobulinemia. CXCR4 mutations are identified in approximately 30% of MYD88L265P cases and have been associated with ibrutinib resistance in clinical trials. Mutations in CD798, ARID1a, or TP53 were described at lower frequency. Deciphering the earliest initiating lesions and identifying the molecular alterations leading to disease progression currently represent important goals in the future to identify the most relevant targets for precision therapy in Waldenstrom macroglobulinemia.