Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2018 Nov;93(11):1420-1426. doi: 10.1002/ajh.25267. Epub 2018 Sep 30.
We examined the influence of mutations and karyotype on conventional treatment response, specifically hematological improvement in anemia, in primary myelodysplastic syndromes (MDS). Cytogenetic and next generation sequencing (NGS)-derived mutation information was available in 357 patients (median age 74 years; 70% males); the revised international prognostic scoring system risk distribution was very high in 11%, high 15%, intermediate 17%, low 40% and very low 16%. At least one mutation was detected in 81% of patients; most frequent were SF3B1 (32%), ASXL1 (27%), TET2 (24%) and U2AF1 (15%). At median follow-up of 24 months, treatment with hypomethylating agents (HMAs) was documented in 121 (34%) patients, lenalidomide (LEN) in 55 (15%), and erythropoiesis stimulating agents (ESAs) in 136 (38%). ASXL1 mutations adversely affected response to HMAs (27% vs 48%; P = 0.02) and LEN (9% vs 43%; P = 0.04), but not ESAs (P = 0.6). LEN response was also adversely affected by U2AF1 mutations (0% vs 42%; P = 0.02) and high risk karyotype (0% vs 41% in intermediate vs 47% in low risk; P = 0.01). Patients with SF3B1 mutations were more likely to respond to LEN (56% vs 27%; P = 0.04). Contrary to previous reports, we found no association between TET2 mutations and HMA treatment response (40% vs 41%; P = 0.9), even in the absence of ASXL1 mutations (P = 0.4).We conclude that ASXL1 mutations in MDS predict inferior response to treatment with both HMAs and LEN; response to LEN was also compromised by U2AF1 mutations and high risk karyotype; SF3B1 mutations identified patients likely to respond to LEN.
我们研究了突变和核型对原发性骨髓增生异常综合征（MDS）常规治疗反应的影响，特别是贫血的血液学改善。357 例患者（中位年龄 74 岁；70%为男性）可获得细胞遗传学和下一代测序（NGS）衍生的突变信息；修订后的国际预后评分系统风险分布为高危 11%、中危 15%、低危 40%和极低危 16%。81%的患者至少检测到一个突变；最常见的是 SF3B1（32%）、ASXL1（27%）、TET2（24%）和 U2AF1（15%）。中位随访 24 个月时，记录到 121 例（34%）患者接受低甲基化剂（HMAs）治疗、55 例（15%）患者接受来那度胺（LEN）治疗、136 例（38%）患者接受促红细胞生成素刺激剂（ESAs）治疗。ASXL1 突变对 HMAs（27% vs 48%；P=0.02）和 LEN（9% vs 43%；P=0.04）的反应产生不良影响，但对 ESA（P=0.6）无影响。U2AF1 突变（0% vs 42%；P=0.02）和高危核型（中危与低危相比分别为 0% vs 41%和 47%；P=0.01）也对 LEN 反应产生不良影响。SF3B1 突变患者更可能对 LEN 有反应（56% vs 27%；P=0.04）。与之前的报告相反，我们发现 TET2 突变与 HMAs 治疗反应之间没有关联（40% vs 41%；P=0.9），即使在没有 ASXL1 突变的情况下也是如此（P=0.4）。我们得出结论，MDS 中的 ASXL1 突变预测对 HMAs 和 LEN 的治疗反应不佳；LEN 的反应也因 U2AF1 突变和高危核型而受损；SF3B1 突变可识别可能对 LEN 有反应的患者。
