文章：

慢性粒单核细胞白血病中的细胞遗传学和分子异常

Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia

原文发布日期：2016-02-05

DOI: 10.1038/bcj.2016.5

类型: Review

开放获取: 是

英文摘要：

Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder associated with peripheral blood monocytosis and an inherent tendency to transform to acute myeloid leukemia. CMML has overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Clonal cytogenetic changes are seen in ~30%, whereas gene mutations are seen in >90% of patients. Common cytogenetic abnormalities include; trisomy 8, -Y, -7/del(7q), trisomy 21 and del(20q), with the Mayo–French risk stratification effectively risk stratifying patients based on cytogenetic abnormalities. Gene mutations frequently involve epigenetic regulators (TET2 ~60%), modulators of chromatin (ASXL1 ~40%), spliceosome components (SRSF2 ~50%), transcription factors (RUNX1 ~15%) and signal pathways (RAS ~30%, CBL ~15%). Of these, thus far, only nonsense and frameshift ASXL1 mutations have been shown to negatively impact overall survival. This has resulted in the development of contemporary, molecularly integrated (inclusive of ASXL1 mutations) CMML prognostic models, including Molecular Mayo Model and the Groupe Français des Myélodysplasies model. Better understanding of the prevalent genetic and epigenetic dysregulation has resulted in emerging targeted treatment options for some patients. The development of an integrated (cytogenetic and molecular) prognostic model along with CMML-specific response assessment criteria are much needed future goals.

摘要翻译： 

慢性粒单核细胞白血病（CMML）是一种克隆性干细胞疾病，其特征为外周血单核细胞增多且具有向急性髓系白血病转化的固有倾向。该疾病兼具骨髓增生异常综合征和骨髓增殖性肿瘤的重叠特征。约30%的患者存在克隆性细胞遗传学改变，而超过90%的患者可检测到基因突变。常见细胞遗传学异常包括：8号染色体三体、Y染色体缺失、7号染色体缺失/7q缺失、21号染色体三体及20q缺失，其中梅奥-法国风险分层系统能基于细胞遗传学异常实现有效风险分层。高频基因突变涉及表观遗传调控因子（TET2约60%）、染色质调节因子（ASXL1约40%）、剪接体组件（SRSF2约50%）、转录因子（RUNX1约15%）及信号通路（RAS约30%，CBL约15%）。截至目前，这些突变中仅ASXL1无义和移码突变被证实对总生存期产生负面影响。这一发现推动了当代整合分子学特征（包含ASXL1突变）的CMML预后模型发展，包括分子梅奥模型和法国骨髓增生异常工作组模型。对普遍存在的遗传学与表观遗传学失调机制的深入理解，为部分患者带来了新兴靶向治疗选择。未来亟需实现的核心目标包括：建立整合细胞遗传学与分子学特征的预后模型，并制定CMML特异性疗效评估标准。

原文链接：

Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia