Clinicopathological characterization of chronic lymphocytic leukemia with MYD88 mutations: L265P and non-L265P mutations are associated with different features

MYD88mutations in chronic lymphocytic leukemia (CLL) are not well characterized. Earlier reports yielded conflicting results in terms of clinicopathologic presentation and prognostic impact ofMYD88mutations in CLL patients. In addition, the morphological and immunophenotypic features of CLL cases carryingMYD88mutations have not been explored. Finally, the clinical or biologic implications of the canonical L265PMYD88mutation vs. mutations in other sites ofMYD88within the context of CLL are also unknown. In this study, a cohort of 1779 CLL patients underwent mutational analysis, and 56 (3.1%) cases were found to haveMYD88mutations, including 38 with L265P mutations (designated here as group A) and 18 with non-L265P mutations (group B). Cases with wild typeMYD88were included as controls. There was no morphological difference in cases with and withoutMYD88mutations. Immunophenotypically, cases with mutatedMYD88(both groups A and B) more frequently had an atypical immunophenotype when compared to wild type cases. Group A patients were younger and were associated with variable favorable prognostic factors, including less elevated beta 2-microglobulin level, negative CD38 and ZAP70, higher frequency of mutatedIGHVand isolated del(13q14.3), and lower frequency of del(11q22.3) and mutations ofNOTCH1andSF3B1. In contrast, group B patients were more similar to CLL patients with wild typeMYD88. There was no difference in time to first treatment when comparingMYD88-mutated vs. wild type CLL patients before and after stratification according toIGHVmutation status. In summary,MYD88mutations are uncommon in CLL and cases with L265P mutation have distinctive clinical, immunophenotypic, cytogenetic, and molecular features. There is no significant impact ofMYD88mutations on time to first treatment in CLL.