Wang Yu-Hung, Lin Chien-Chin, Yao Chi-Yuan, Hsu Chia-Lang, Hou Hsin-An, Tsai Cheng-Hong, Chou Wen-Chien, Tien Hwei-Fang
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; and.
Division of Hematology, Department of Internal Medicine.
Blood Adv. 2020 Feb 25;4(4):644-654. doi: 10.1182/bloodadvances.2019001185.
Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given.
骨髓增生异常综合征（MDS）是一组异质性疾病。即使在相同风险组中，患者的预后也有所不同。因此，寻找新的预后标志物很有必要。白血病干细胞（LSCs）是白血病化疗耐药和复发的原因。最近，发现与LSCs干性相关的17个基因的表达与急性髓系白血病患者的预后相关。然而，LSC基因表达在MDS（一种由造血干细胞引起的疾病）中的临床影响仍不清楚。我们分析了原发性MDS患者中17个与干性相关基因的表达谱，发现4个基因（LAPTM4B、NGFRAP1、EMP1和CPXM1）的表达与总生存期（OS）显著相关。我们基于这4个基因表达的加权和构建了一个LSC4评分系统，并探讨了其在MDS患者中的临床意义。较高的LSC4评分与较高的修订国际预后评分系统（IPSS-R）评分、复杂核型以及RUNX1、ASXL1和TP53突变相关。高分患者的OS和无白血病生存期（LFS）显著缩短，这在2个独立的验证队列中也得到了证实。亚组分析显示，LSC4评分对OS的预后意义在IPSS-R低风险和高风险组中均有效。此外，在多变量分析中，较高的LSC4评分是OS和LFS的独立不良风险因素。总之，LSC4评分可以独立预测MDS患者的预后，而不考虑IPSS-R风险，可用于指导MDS患者的治疗，尤其是通常仅给予支持治疗的低风险组患者。
