Marsh J C W, Mufti G J
Department of Haematological Medicine, King's College Hospital London and King's College London, Denmark Hill, London, SE59RS, UK.
Int J Hematol. 2016 Aug;104(2):159-67. doi: 10.1007/s12185-016-1972-8. Epub 2016 Mar 18.
Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.
再生障碍性贫血（AA）常与其他克隆性造血疾病相关，如阵发性睡眠性血红蛋白尿（PNH）、骨髓增生异常综合征（MDS）和T大颗粒淋巴细胞增多症。某些克隆可能在骨髓环境中逃避免疫攻击并增殖，相对于正常造血干细胞获得生存优势，如8号染色体三体、6号染色体短臂杂合性缺失和13q缺失克隆。最近报道，在约20%-25%的AA患者中存在除外PNH克隆的获得性体细胞突变（SM），这使患者后期发生向MDS/急性髓系白血病恶性转化的风险更高。此外，某些SM，如ASXL1和DNMT3A与免疫抑制治疗后的不良生存相关，而PIGA、BCOR/BCORL1则预示良好的反应和生存。需要对AA的免疫特征进行更详细的系列分析，以了解相当比例患者中存在带SM克隆的发病机制基础。
