Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes. Issue 2 (24th December 2019)

• Record Type: Journal Article
• Authors: Jiang, Lingxu; Luo, Yingwan; Zhu, Shuanghong; Wang, Lu; Ma, Liya; Zhang, Hua; Shen, Chuying; Yang, Wenli; Ren, Yanling; Zhou, Xinping; Mei, Chen; Ye, Li; Xu, Weilai; Yang, Haiyang; Lu, Chenxi; Jin, Jie; Tong, Hongyan
• Is Part Of: Cancer science. Volume 111:Issue 2(2020)
• Page Start: 580
• Page End: 591
• Publication Date: 2019-12-24
• Subjects: lower‐risk myelodysplastic syndromes -- mutation burden -- mutation status -- prognosis -- variant allele frequency; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14270
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 ( P = .001), RUNX1 ( P = .031), EZH2 ( P = .049), TP53 ( P = .016), SRSF2 ( P = .046), JAK2 ( P = .040), and IDH2 ( P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 ( P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 ( P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 ( P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% ( P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased ( P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups ( P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment. Abstract : Shorter OS was associated with mutation status of ASXL1, EZH2 and JAK2, as well as TET2 VAF ≥18%. A novel prognostic scoring system based on the IPSS and the presence/absence of the four independent mutational factors further stratified LR‐MDS patients into three prognostically different groups. Integration of IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment.