Given the poor outcome of refractory and relapsing T-cell acute lymphoblastic leukemia (T-ALL), identifying prognostic markers is still challenging. Using SNP array analysis, we provide a comprehensive analysis of genomic imbalances in a cohort of 317 newly diagnosed patients with T-ALL including 135 children and 182 adults with respect to clinical and biological features and outcomes. SNP array results identified at least 1 somatic genomic imbalance in virtually all patients with T-ALL (∼96%). Del(9)(p21) (∼70%) and UPD(9)p21)// (∼28%) were the most frequent genomic imbalances. Unexpectedly del(13q14)// (∼14%) was the second-most frequent copy number variants followed by del(6)(q15)/ (∼11%), del(1)(p33)/- (∼11%), del(12)(p13)/ (∼9%), del(18)(p11)/ (∼9%), del(1)(p36)/ (∼9%), and del(17)(q11)// (∼8%). SNP array also revealed distinct profiles of genomic imbalances according to age, immunophenotype, and oncogenetic subgroups. In particular, adult patients with T-ALL demonstrated a significantly higher incidence of del(1)(p36)/, and del(13)(q14)//, and lower incidence of del(9)(p21) and UPD(9p21)//. We determined a threshold of 15 genomic imbalances to stratify patients into high- and low-risk groups of relapse. Survival analysis also revealed the poor outcome, despite the low number of affected cases, conferred by the presence of chromothripsis (n = 6, ∼2%), del(16)(p13)/ (n = 15, ∼5%) as well as the newly-identified recurrent gain at 6q27 involving (n = 10, ∼3%). Genomic complexity, del(16)(p13)/ and gain at 6q27 involving , maintained their significance in multivariate analysis for survival outcome. Our study thus demonstrated that whole genome analysis of imbalances provides new insights to refine risk stratification in T-ALL.

中文翻译：

---

基因组失衡分析为成人和儿童 T-ALL 的预后因素提供了新的见解

鉴于难治性和复发性 T 细胞急性淋巴细胞白血病 (T-ALL) 的预后不佳，确定预后标志物仍然具有挑战性。利用 SNP 阵列分析，我们对 317 名新诊断的 T-ALL 患者（包括 135 名儿童和 182 名成人）的基因组失衡的临床和生物学特征及结果进行了全面分析。 SNP 阵列结果在几乎所有 T-ALL 患者 (∼96%) 中发现了至少 1 种体细胞基因组失衡。 Del(9)(p21) (∼70%) 和 UPD(9)p21)// (∼28%) 是最常见的基因组失衡。出乎意料的是，del(13q14)// (∼14%) 是第二常见的拷贝数变异，其次是 del(6)(q15)/ (∼11%)、del(1)(p33)/- (∼11%) )、del(12)(p13)/ (∼9%)、del(18)(p11)/ (∼9%)、del(1)(p36)/ (∼9%) 和 del(17)( q11) // (∼8%). SNP 阵列还根据年龄、免疫表型和致癌亚组揭示了基因组失衡的不同特征。特别是，成年 T-ALL 患者表现出 del(1)(p36)/ 和 del(13)(q14)// 的发生率显着较高，而 del(9)(p21) 和 UPD(9p21) 的发生率较低）//。我们确定了 15 种基因组失衡的阈值，将患者分为复发高风险组和低风险组。生存分析还显示，尽管受影响病例数量较少，但由于存在染色体碎裂，生存分析结果较差（n = 6，∼2%），del(16)(p13)/（n = 15，∼5%）以及新确定的 6q27 经常性增益涉及 (n = 10, ∼3%)。涉及 的基因组复杂性、del(16)(p13)/ 和 6q27 的增益在生存结果的多变量分析中保持了显着性。因此，我们的研究表明，全基因组失衡分析为细化 T-ALL 风险分层提供了新的见解。