当前位置: X-MOL 学术Leukemia › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7.
Leukemia ( IF 11.4 ) Pub Date : 2020-02-17 , DOI: 10.1038/s41375-020-0728-x
Elena Crisà 1, 2, 3 , Austin G Kulasekararaj 1 , Vera Adema 4, 5 , Esperanza Such 6, 7 , Julie Schanz 8 , Detlef Haase 8 , Katayoon Shirneshan 8 , Steven Best 9 , Syed A Mian 1, 10 , Aytug Kizilors 9 , José Cervera 11 , Nicholas Lea 9 , Dario Ferrero 3, 12 , Ulrich Germing 13 , Barbara Hildebrandt 14 , Ana Belén Valencia Martínez 15 , Valeria Santini 3, 15 , Guillermo F Sanz 6, 7, 16 , Francesc Solé 4 , Ghulam J Mufti 1
Affiliation  

Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequency between the two groups. Patients harbouring ≥2 mutations had a worse outcome than patients with <2 or no mutations (leukaemic transformation at 24 months, 38% and 20%, respectively, p = 0.044). Untreated patients with del(7q) had better overall survival (OS) compared with -7 (median OS, 34 vs 17 months, p = 0.034). In multivariable analysis, blast count, TP53 mutations and number of mutations were independent predictors of OS, whereas the cytogenetic subgroups did not retain prognostic relevance. This study highlights the importance of mutational analysis in terms of prognosis in MDS patients with isolated -7 or del(7q).

中文翻译:

体细胞突变对孤立性部分或全部7号染色体丢失的骨髓增生异常患者的影响。

在骨髓增生异常综合症(MDS)中,单体7 [-7]和/或7号染色体的部分缺失[del(7q)]与不良和中期预后相关,但体细胞突变也可能起关键的互补作用。我们分析了对280例-7 / del(7q)的MDS患者进行深靶向突变筛选的结果的影响,这些患者是孤立的细胞遗传学异常(del(7q)为86,-7为194)。del(7q)或-7的患者具有相似的人口统计学和疾病相关特征。在79%(93/117)的患者中检测到体细胞突变(-7%的患者为82%,del(7q)组的患者为73%)。每位患者的突变中位数为2(范围0-8)。两组之间的突变频率没有差异。携带≥2个突变的患者的结果要比没有<2个突变或没有突变的患者(24个月白血病转化,分别为38%和20%,p = 0.044)。未经治疗的del(7q)患者的总生存期(OS)比-7更好(中位OS,34 vs 17个月,p = 0.034)。在多变量分析中,胚盘计数,TP53突变和突变数量是OS的独立预测因子,而细胞遗传学亚组则没有保留预后相关性。这项研究突出了突变分析对孤立的-7或del(7q)的MDS患者的预后的重要性。
更新日期:2020-02-18
down
wechat
bug