The association of complex genetic background with the prognosis of acute leukemia with ambiguous lineage.
The association of complex genetic background with the prognosis of acute leukemia with ambiguous lineage.
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DOI：
10.1038/s41598-021-03709-7
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发表时间：
2021-12-21
影响因子：
4.6
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Huang J;Zhou J;Xiao M;Mao X;Zhu L;Liu S;Li Q;Wang J;Zhou J;Cai H;Wang G
谱系不清的急性白血病（ALAL）是一种罕见的高度侵袭性恶性肿瘤，其分子特征和治疗建议有限。在这项研究中，我们回顾性分析了我中心2012年1月至2018年6月的1635例急性白血病病例。ALAL的诊断基于EGIL或2016 WHO标准，共纳入39例患者。4例患者经两种分类系统诊断为急性未分化白血病（AUL）。在接受高通量测序的患者中，89.5%检测到至少一个突变，每个样本的基因突变中位数为3（0-8）。最常见的突变基因是NRAS（4，21%），CEBPA（4，21%），JAK 3（3，16%），RUNX 1（3，16%）。混合表型急性白血病（MPAL）中检测到的突变主要集中在基因组稳定性和转录调控相关基因上，而AUL则主要集中在信号通路相关基因上。生存分析结果表明，突变负荷可能对预测ALAL的临床结局具有重要作用。此外，根据WHO标准排除的患者的临床结局比纳入的患者更差。原始细胞遗传复杂性与临床结局的相关性以及WHO系统诊断标准的合理性有待于更大规模的前瞻性临床研究进行评价。
Acute leukemia with ambiguous lineage (ALAL) is a rare and highly aggressive malignancy with limited molecular characterization and therapeutic recommendations. In this study, we retrospectively analyzed 1635 acute leukemia cases in our center from January 2012 to June 2018. The diagnose of ALAL was based on either EGIL or 2016 WHO criteria, a total of 39 patients were included. Four patients diagnosed as acute undifferentiated leukemia (AUL) by both classification systems. Among the patients underwent high-throughput sequencing, 89.5% were detected at least one mutation and the median number of gene mutation was 3 (0–8) per sample. The most frequently mutated genes were NRAS (4, 21%), CEBPA (4, 21%), JAK3 (3, 16%), RUNX1 (3, 16%). The mutations detected in mixed-phenotype acute leukemia (MPAL) enriched in genes related to genomic stability and transcriptional regulation; while AUL cases frequently mutated in genes involved in signaling pathway. The survival analysis strongly suggested that mutation burden may play important roles to predict the clinical outcomes of ALAL. In addition, the patients excluded by WHO criteria had even worse clinical outcome than those included. The association of the genetic complexity of blast cells with the clinical outcomes and rationality of the diagnostic criteria of WHO system need to be evaluated by more large-scale prospective clinical studies.
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影响因子：
20.3
作者：
Vardiman, James W.;Thiele, Juergen;Bloomfield, Clara D.
通讯作者：
Bloomfield, Clara D.
影响因子：
10.1
作者：
Munker R;Labopin M;Esteve J;Schmid C;Mohty M;Nagler A
通讯作者：
Nagler A
影响因子：
4.1
作者：
McCall, Chad M.;Mosier, Stacy;Eshleman, James R.
通讯作者：
Eshleman, James R.
影响因子：
2.2
作者：
Pomerantz A;Rodriguez-Rodriguez S;Demichelis-Gomez R;Barrera-Lumbreras G;Barrales-Benitez O;Lopez-Karpovitch X;Aguayo-Gonzalez A
通讯作者：
Aguayo-Gonzalez A
影响因子：
3.5
作者：
Weinberg, Olga K.;Seetharam, Mahesh;Arber, Daniel A.
通讯作者：
Arber, Daniel A.