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首页> 外文期刊>Pediatric blood & cancer >High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6‐RUNX1 ETV6‐RUNX1 ‐positive acute lymphoblastic leukemia
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High sensitivity and clonal stability of the genomic fusion as single marker for response monitoring in ETV6‐RUNX1 ETV6‐RUNX1 ‐positive acute lymphoblastic leukemia

机译：基因组融合的高敏感性和克隆稳定性作为etv6-runx1 etv6-runx1-阳性急性淋巴细胞白血病响应监测的单个标记

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Abstract Background Assessment of minimal residual disease (MRD) is an integral component for response monitoring and treatment stratification in acute lymphoblastic leukemia (ALL). We aimed to evaluate the genomic ETV6‐RUNX1 fusion sites as a single marker for MRD quantification. Procedure In a representative, uniformly treated cohort of pediatric relapsed ALL patients ( n ?=?52), ETV6‐RUNX1 fusion sites were compared to the current gold standard, immunoglobulin/T‐cell receptor (Ig/TCR) gene rearrangements. Results Primer/probe sets designed to ETV6‐RUNX1 fusions achieved significantly more frequent a sensitivity and a quantitative range of at least 10 –4 compared to the gold standard with 100% and 73%?versus 76% and 47%, respectively. The breakpoint sequence was identical at diagnosis and relapse in all tested cases. There was a high degree of concordance between quantitative MRD results assessed using ETV6‐RUNX1 and the highest Ig/TCR marker (Spearman's 0.899, P ??.01) with differences?? log‐step in only 6% of patients. A high proportion of ETV6‐RUNX1‐ positive ALL relapses (40%) in our cohort showed a poor response to induction treatment at relapse, and therefore had an indication for hematopoietic stem cell transplantation, demonstrating the need of accurate identification of this subgroup. Conclusions ETV6‐RUNX1 fusion sites are highly sensitive and reliable MRD markers. Our data confirm that they are unaffected by clonal evolution and selection during front‐line and second‐line chemotherapy in contrast to Ig/TCR rearrangements, which require several markers per patient to compensate for the observed loss of target clones. In future studies, the genomic ETV6‐RUNX1 fusion can be used as single MRD marker.
机译：摘要最小残留疾病（MRD）的背景评估是急性淋巴细胞白血病（全部）中的反应监测和治疗分层的一体组分。我们旨在评估基因组EtV6-RUNX1融合位点作为MRD量化的单个标记。程序在一个代表性的，儿科的均匀处理队列复发性ALL患者（n =？52），ETV6-RUNX1融合位点相比，目前金标准，免疫球蛋白/ T细胞受体球蛋白（Ig / TCR）基因重排。结果设计为ETV6-RUNX1融合的底漆/探针组频繁频繁频繁，与金标准相比，至少10-4的定量范围，分别与76％和47％分别相比。断点序列在所有测试案例中的诊断和复发时相同。使用ETV6-RONX1和最高IG / TCR标记（Spearman的0.899，P≤01）评估的定量MRD结果之间存在高度的一致性差异？＆gt ;?只有6％的患者登录。我们的队列中的高etv6-runx1-阳性均复活（40％）表现出对复发治疗的良好反应，因此表明造血干细胞移植的指示，表明需要准确鉴定该亚组。结论ETV6-RUNX1融合位点是高度敏感和可靠的MRD标记。我们的数据确认，它们在前线和二线化疗期间不受克隆演化和选择的影响，与IG / TCR重排相比，每位患者需要几个标记来补偿观察到的目标克隆的损失。在未来的研究中，基因组ETV6-RUNX1融合可以用作单个MRD标记。

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