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MYD88  mutations in chronic lymphocytic leukemia (CLL) are not well characterized. Earlier reports yielded conflicting results in terms of clinicopathologic presentation and prognostic impact of  MYD88  mutations in CLL patients. In addition, the morphological and immunophenotypic features of CLL cases carrying  MYD88  mutations have not been explored. Finally, the clinical or biologic implications of the canonical L265P  MYD88  mutation vs. mutations in other sites of  MYD88  within 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 have  MYD88  mutations, including 38 with L265P mutations (designated here as group A) and 18 with non-L265P mutations (group B). Cases with wild type  MYD88  were included as controls. There was no morphological difference in cases with and without  MYD88  mutations. Immunophenotypically, cases with mutated  MYD88  (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 β2-microglobulin level, negative CD38 and ZAP70, higher frequency of mutated  IGHV  and isolated del(13q14.3), and lower frequency of del(11q22.3) and mutations of  NOTCH1  and  SF3B1 . In contrast, group B patients were more similar to CLL patients with wild type  MYD88 . There was no difference in time to first treatment when comparing  MYD88 -mutated vs. wild type CLL patients before and after stratification according to  IGHV  mutation status. In summary,  MYD88  mutations are uncommon in CLL and cases with L265P mutation have distinctive clinical, immunophenotypic, cytogenetic, and molecular features. There is no significant impact of  MYD88  mutations on time to first treatment in CLL.

blood cancer journal

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