Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory-specific incidence and prognostic impact among 348 informative cases
Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory-specific incidence and prognostic impact among 348 informative cases
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DOI：
10.1002/ajh.25265
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发表时间：
2018-12-01
影响因子：
12.8
通讯作者：
Tefferi, Ayalew
中科院分区：
文献类型：
--
作者：
Shah, Sahrish;Pardanani, Animesh;Tefferi, Ayalew
世界卫生组织（WHO）系统列出了系统性肥大细胞增多症（SM）的五种形态分类：惰性（ISM）、阴烧、SM伴血液学肿瘤（SM- ahn）、侵袭性（ASM）和肥大细胞白血病（MCL）。最近的研究强调了SM突变的预后重要性，包括ASXL1、RUNX1和SRSF2。相比之下，关于SM中细胞遗传学异常的发生率及其预后相关性的信息，特别是在突变的背景下，是有限的。在本研究中，我们回顾性回顾了348例SM患者的细胞遗传学结果（中位年龄59岁，53%男性）；ISM占41%，SM-AHN占45%，ASM占14%，MCL占2例。核型异常53例（15%），其中ISM发生率为6%，SM-AHN发生率为26%，ASM发生率为8% (P < 0.001)；在SM-AHN病例中，淋巴型SM-AHN异常发生率为0%，髓型SM-AHN异常发生率为28% （P < 0.001）。临床相关研究显示，核型异常与男性（P = 0.002）、年龄（P = 0.04）、血小板减少（P < 0.001）和贫血（P < 0.001）有显著相关性，但与不良突变的存在无显著相关性（P = 0.19）。在单因素分析中，异常核型与较差的生存率相关（HR 3.0, 95% CI 2.0-4.3），特别是ASM （HR 4.9, 95% CI 1.1-16.1）和SM-AHN （HR 1.8, 95% CI 1.2-2.7）。样本量充足允许对sm - ahn -髓系进行额外的多变量分析，揭示了不良突变（P = 0.003）、贫血（P = 0.003）和血小板减少（P = 0.001）对预后的独立贡献，但与异常核型无关（P = 0.31）。我们的观察结果表明，在SM中，突变比核型更具有预后相关性。
The World Health Organization (WHO) system lists five morphological categories of systemic mastocytosis (SM): indolent (ISM), smoldering, SM with an associated hematological neoplasm (SM-AHN), aggressive (ASM) and mast cell leukemia (MCL). Recent studies have highlighted the prognostic importance of mutations in SM, including ASXL1, RUNX1, and SRSF2. In contrast, information on incidence of cytogenetic abnormalities in SM and their prognostic relevance, especially in the context of mutations, is limited. In the current study, we retrospectively reviewed the cytogenetic findings in 348 consecutive cases of SM (median age 59 years; 53% males); 41% constituted ISM, 45% SM-AHN, 14% ASM and two cases of MCL. Karyotype was abnormal in 53 (15%) cases with incidences of 6% for ISM, 26% for SM-AHN and 8% for ASM (P < .001); among SM-AHN cases, abnormal karyotype incidences were 0% for SM-AHN-lymphoid and 28% for SM-AHN-myeloid (P < .001). Clinical correlative studies disclosed significant associations between abnormal karyotype and male sex (P = .002), age > 60 years (P = .04), thrombocytopenia (P < .001) and anemia (P < .001), but not with the presence of adverse mutations (P = .19). In univariate analysis, abnormal karyotype was associated with inferior survival (HR 3.0, 95% CI 2.0-4.3), specifically confirmed for ASM (HR 4.9, 95% CI 1.1-16.1) and SM-AHN (HR 1.8, 95% CI 1.2-2.7). Sample size adequacy allowed additional multivariable analysis in SM-AHN-myeloid, which disclosed independent prognostic contribution from adverse mutations (P = .003), anemia (P = .003) and thrombocytopenia (P = .001), but not from abnormal karyotype (P = .31). Our observations suggest that mutations are prognostically more relevant than karyotype in SM.