Genomic heterogeneity contributed to different prognosis between adult and pediatric acute lymphoblastic.
Genomic heterogeneity contributed to different prognosis between adult and pediatric acute lymphoblastic.
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基因组异质性导致成人和儿童急性淋巴细胞的预后不同。
DOI：
10.1002/jlb.5a0721-361r
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发表时间：
2022
影响因子：
5.5
通讯作者：
胡建达
中科院分区：
文献类型：
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作者：
陈艳欣;郑湧智;洪允达;温晶晶;李佳蒸;黄燕;陈溢;郑晓云;杨婷;徐杨棋;郑静;胡建达
成人急性淋巴细胞白血病（ALL）的预后不如儿童。因此，在成人中治愈ALL仍然具有挑战性。尽管成人和儿童ALL的差异基因改变模式尚未在全基因组范围内全面确定，但在ALL中已观察到异常遗传改变。我们研究了成人（n= 64）和儿童（n= 54） ALL患者基因组图谱的生物学差异以及基因组异质性与预后的关系。这两个人群显示出相似的常见突变类型，但在成人ALL中遗传改变的患病率增加。在成人和儿童ALL中，每个样本的基因突变中位数分别为17个（范围：1-53）和4.5个（范围：1-19）（p< 0.001）。基因突变数增加与年龄显著相关（R2= 0.5853,p< 0.001）。我们在成人和儿童ALL样本中分别鉴定出122和53个驱动基因。成年ALL患者中IKZF1、IDH1和ttn突变显著富集。KRAS、ARID1A和crebbp突变在ALL患儿中显著富集（p< 0.05）。成人和儿童ALL患者的复发率分别为40.0%和9.6% （p= 0.003）。成人ALL患者的总生存期和无复发生存期均低于儿科ALL患者（p= 0.002和p< 0.001）。这一基因组图谱增强了对两个人群之间ALL生物学差异的理解，并为开发治疗方法提供了见解。
The prognosis of acute lymphoblastic leukemia (ALL) in adults is inferior to that in children. Hence, ALL remains challenging to cure in the adult population. Aberrant genetic alterations have been observed in ALL, although the patterns of differential gene alterations in adult and pediatric ALL have not been comprehensively determined on a genome-wide scale. We investigated the biologic differences in genomic profiles between adults (n= 64) and children (n= 54) with ALL and relationship between genomic heterogeneity and prognosis. The 2 populations showed similar common mutation types but an increased prevalence of genetic alterations in adult ALL. The median numbers of gene mutations were 17 (range: 1–53) and 4.5 (range: 1–19) per sample in adult and pediatric ALL, respectively (p< 0.001). An increased number of gene mutations and age were significantly correlated (R2= 0.5853,p< 0.001). We identified 122 and 53 driver genes in adult and pediatric ALL samples, respectively.IKZF1, IDH1, andTTNmutations were significantly enriched in adult patients with ALL.KRAS, ARID1A, andCREBBPmutations were significantly enriched in pediatric patients with ALL (p< 0.05). The incidence of relapse was 40.0% and 9.6% in adult and pediatric patients with ALL, respectively (p= 0.003). The overall survival and relapse-free survival of adult patients with ALL were poorer than those of pediatric patients with ALL (p= 0.002 andp< 0.001, respectively). This genomic landscape enhances the understanding of the biologic differences in ALL between the 2 populations and provides insight for developing therapeutic approaches.