真实世界队列中低风险骨髓发育异常综合征（MDS）患者基因动态频率、模式及预后影响的全面序贯遗传分析

Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real-world cohort of patients with lower-risk MDS

HemaSphere

影响因子:14.6

分区:医学3区 / 血液学3区

发表日期:2024 Sep

作者: Paolo Mazzeo, Christina Ganster, John Wiedenhöft, Katayoon Shirneshan, Katharina Rittscher, Elzbieta B Brzuszkiewicz, Doris Steinemann, Maximilian Schieck, Catharina Müller-Thomas, Hannes Treiber, Friederike Braulke, Ulrich Germing, Katja Sockel, Ekaterina Balaian, Julie Schanz, Uwe Platzbecker, Katharina S Götze, Detlef Haase

DOI: 10.1002/hem3.70014

摘要

次级遗传病变（克隆进化，CE）和/或现有克隆的扩增（CEXP）促成了骨髓发育不良综合征（MDS）中的克隆动态（CD）。尽管CD在高危患者中在疾病进展和转变为急性髓系白血病（AML）中起重要作用，但由于缺乏考虑到疾病长期临床稳定过程的稳健纵向数据，对低危MDS（LR-MDS）患者的CD知之甚少。在本回顾性分析中，我们描绘了未筛选的真实世界LR-MDS患者队列中CD的发生频率及其预后影响。筛查了68例患者，随访中位40.5个月，利用染色体带状分析、荧光原位杂交、测序及分子核型分析检测到的CE和CEXP事件共计发生47次，平均每4年发生1次事件。值得注意的是，发生至少1次CE事件的患者更可能接受后续治疗。令人意外的是，CE未与较差的预后显著相关，合理解释为CE检测促使开始了疾病修饰治疗。

Abstract

The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients. We screened 68 patients with a median follow-up of 40.5 months and a median of 7.5 (range: 2-22) timepoints for CE and CEXP detected by chromosomal banding analysis, fluorescence in situ hybridization, sequencing, and molecular karyotyping. In 30/68 patients, 47 CE events and a CD rate of 1 event per 4 years were documented. Of note, patients with at least 1 CE event had an increased probability for subsequent treatment. Unexpectedly, CE did not correlate with inferior outcomes, which could be reasonably explained by CD detection triggering the subsequent start of a disease-modifying therapy.