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NUP98 重排导致了儿科急性髓系白血病原代诱导失败的候选生物标志物的鉴定。

NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia.

机构信息

Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy.

Cytogenetic-Cytofluorimetric-Molecular Biology Lab, 95123 Catania, Italy.

出版信息

Int J Mol Sci. 2021 Apr 27;22(9):4575. doi: 10.3390/ijms22094575.

DOI:10.3390/ijms22094575
PMID:33925480
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8123909/
Abstract

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for "Differentially Expressed Genes" (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: , , , , , , , and . In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.

摘要

急性髓系白血病的常规化疗方案通常包括强化诱导期，以达到骨髓中原始细胞(<5%)形态学缓解。大多数病例被归类为原发性诱导缓解（PIR）；然而，15%的儿童无法缓解，被定义为原发性诱导失败（PIF）。本研究旨在对 PIF 儿童的急性髓系白血病（AML）的基因表达谱进行特征分析，以检测分子途径功能障碍并确定潜在的生物标志物。鉴于 NUP98 重排在 PIF-AML 患者中富集，我们研究了原发性耐药中 NUP98 驱动基因的相关性。因此，对 GEO 数据库中 85 个表达谱和 TARGET 计划中的 358 个 RNAseq AML 样本进行了“差异表达基因”（DEGs）分析，以确定 NUP98+和 NUP98-之间的差异，鉴定出 110 个高度可信的 NUP98/PIF 相关 DEGs。我们通过 qRT-PCR 验证了在 PIF 患者的本地队列中，根据诊断准确性选择的九个 DEGs 的过表达： 、 、 、 、 、 、 和 。总之，NUP98 突变分析和转录组谱的综合分析确定了预测 AML 中 PIF 的新潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71a0/8123909/9405b39c02ab/ijms-22-04575-g006.jpg
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