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哥伦比亚两个癌症中心儿科急性髓细胞白血病患者队列的基因组改变。

Genomic alterations in a cohort of pediatric acute myeloid leukemia patients at two cancer centers in Colombia.

机构信息

Grupo de Patología Molecular, Universidad Nacional de Colombia, Bogotá D.C., Colombia.

Servicios Médicos Yunis Turbay Y Cía S.A.S., Instituto de Genética, Calle 86B # 49D-28, Of 305, Bogotá D.C., Colombia.

出版信息

Int J Hematol. 2023 Feb;117(2):269-277. doi: 10.1007/s12185-022-03475-w. Epub 2022 Oct 24.

Abstract

Few studies identifying genomic aspects in pediatric acute myeloid leukemia patients in Latin American countries have been reported. The aim of this study was to identify genomic alterations, clinical characteristics and outcomes in a cohort of pediatric AML patients. This descriptive observational cohort study included patients with confirmed de novo acute myeloid leukemia up to 18 years of age. Cytogenetics and conventional FISH analysis, next-generation sequencing and PCR testing were performed. The correlation of genomic data with treatment response and outcomes were analyzed. Of the 51 patients analyzed, 67.4% had a cytogenetic abnormality and 74.5% had a genetic variant. FLT3 variants (ITD or TKD D835) were found in 27.4%, followed by NRAS (21.6%), KRAS (13.7%) and WT1 and KIT (11.8%). Patients were stratified by risk (66.6% high-risk) after the end of induction. FLT3-ITD was associated with relapse (OR 11.25; CI 1.89-66.72, p 0.006) and NRAS with death during induction (OR 16.71; CI 1.51-184.59, p 0.022). Our study highlights the importance of rapid incorporation of genetic testing in pediatric AML in Colombia, as it directly affects treatment decisions and outcomes. Incorporation of targeted therapies with conventional chemotherapy is an increasingly urgent need in pediatric patients.

摘要

在拉丁美洲国家,鲜有针对儿科急性髓系白血病患者的基因组研究报告。本研究旨在确定儿科急性髓系白血病患者队列中的基因组改变、临床特征和结局。本研究采用描述性观察性队列设计,纳入了确诊为初发急性髓系白血病且年龄不超过 18 岁的患者。进行了细胞遗传学和常规 FISH 分析、下一代测序和 PCR 检测。分析了基因组数据与治疗反应和结局的相关性。在分析的 51 例患者中,67.4%存在细胞遗传学异常,74.5%存在基因突变。FLT3 变异(ITD 或 TKD D835)占 27.4%,其次是 NRAS(21.6%)、KRAS(13.7%)和 WT1 和 KIT(11.8%)。诱导结束后,患者根据风险(66.6%为高危)进行分层。FLT3-ITD 与复发相关(OR 11.25;CI 1.89-66.72,p 0.006),NRAS 与诱导期间死亡相关(OR 16.71;CI 1.51-184.59,p 0.022)。本研究强调了在哥伦比亚迅速开展儿科急性髓系白血病基因检测的重要性,因为它直接影响治疗决策和结局。在儿科患者中,将靶向治疗与常规化疗结合使用是一项日益紧迫的需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f9/9889450/44d460e907aa/12185_2022_3475_Fig1_HTML.jpg

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