MYD88 mutations predict unfavorable prognosis in Chronic Lymphocytic Leukemia patients with mutated IGHV gene

Qin, Shuchao; Xia, Yi; Miao, Yi; Zhu, Huayuan; Wu, Jia‐Zhu; Fan, Lei; Li, Jianyong; Xu, Wei; Qiao, Chun

doi:10.1038/s41408-017-0014-y

Cited by 19 publications

(22 citation statements)

References 16 publications

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“…Similar results with no prognostic difference in CLL with MYD88 mutations were described in several other studies 24 , 31 , 37 . On the contrary, in a study by Qin et al, MYD88 mutations predicted an unfavorable prognosis in patients with mutated IGHV gene 27 . In our study, although L265P mutation was associated with several favorable prognostic factors, we did not find a difference in TTFT among patients with wild type vs. mutated MYD88 .…”

Section: Discussionmentioning

confidence: 81%

“…Of note, the prior treatment, tumor burden and the assays used to detect the mutations likely contribute to the variable mutation rates reported in different studies. In addition, the prevalence of MYD88 mutations in CLL seems to be higher in Asian population 26 , 27 .…”

Section: Discussionmentioning

confidence: 96%

“…In earlier reports, the relationship of MYD88 mutations to age in CLL has been controversial. Martinez-Trillos et al studied 23 patients with Toll-like receptor ( TLR)/MYD88 mutations and found that mutated patients were significantly younger (median age, 47 years) than unmutated patients (median age, 61 years) 23 , whereas in another two studies by Baliakas et al 28 and Qin et al 27 , the authors showed no age difference. Of note, all these studies lumped different MYD88 mutations as one group.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the inconsistent findings in previous studies about age are likely attributable to combining all mutated cases together as a single group. Previous studies on the prognostic impact of MYD88 mutations in CLL also have been discordant, as some studies showed a favorable outcome 23 whereas others showed an unfavorable prognosis 27 , and yet others showed no prognostic significance 24 , 28 . In the study by Martinez-Trillos et al the authors found that TLR/MYD88 -mutated CLL was seen in a group of young patients with advanced stage at presentation, associated with mutated IGHV , with less ZAP-70 and CD38 expressions and a better OS 23 .…”

Section: Discussionmentioning

confidence: 99%

“…The mutation allelic frequency does not significantly change in sequential CLL samples from the same patients 31 . The outcome of CLL patients with MYD88 mutations is highly controversial; some studies showed a favorable prognosis 23 , 32 whereas others showed an unfavorable prognosis 27 , or no association with prognosis 24 , 28 . Thus, the prognostic role of MYD88 in CLL/SLL is still not established.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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