文章：

MYD88突变慢性淋巴细胞白血病的临床病理特征：L265P与非L265P突变具有不同的相关特征

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

原文发布日期：2020-08-26

DOI: 10.1038/s41408-020-00351-w

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

慢性淋巴细胞白血病（CLL）中的MYD88突变尚未得到充分表征。早期研究关于CLL患者MYD88突变的临床病理表现及预后影响得出了相互矛盾的结果。此外，携带MYD88突变的CLL病例其形态学和免疫表型特征尚未被探讨。最后，在CLL背景下，经典L265P MYD88突变与MYD88其他位点突变在临床或生物学意义上的差异亦不明确。本研究对1779例CLL患者队列进行突变分析，发现56例（3.1%）存在MYD88突变，其中38例为L265P突变（设为A组），18例为非L265P突变（B组）。以MYD88野生型病例作为对照。结果显示MYD88突变型与野生型病例间无形态学差异。免疫表型方面，与野生型相比，MYD88突变型（A组与B组）更常出现非典型免疫表型。A组患者更年轻，且伴随多种有利预后因素，包括β2-微球蛋白升高程度较轻、CD38与ZAP70阴性、IGHV突变频率更高及孤立性del(13q14.3)更高发，同时del(11q22.3)与NOTCH1、SF3B1突变频率较低。相比之下，B组患者特征更接近MYD88野生型CLL患者。根据IGHV突变状态分层前后对比，MYD88突变型与野生型CLL患者的首次治疗时间无显著差异。综上所述，MYD88突变在CLL中较为罕见，其中L265P突变病例具有独特的临床、免疫表型、细胞遗传学和分子学特征，而MYD88突变对CLL患者的首次治疗时间无显著影响。

原文链接：

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