Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age of 68 in clinical diagnosis. About 60% patients are over 60 years old. There are various treatment options for AML patients. But for elderly patients, the complete remission rates are disappointing due to genetic, molecular, and age-related factors. Development of next-generation sequencing technologies makes it possible to seek individual strategies for patients in different ages. This study analyzed transcriptome profiles in platelets of AML patients in different ages for the first time. Platelet RNA sequencing in AML of ten elderly and seven young patients were performed with Illumina TruSeq Stranded mRNA library Prep Kit and Illumina HiSeq4000 sequencing instrument. With the FASTQ sequencing data obtained, statistical analyses between elderly with young AML patients were analyzed by R program. GO and KEGG enrichment analyses were performed via R package clusterProfiler. TOP 10 down-regulated/up-regulated genes in elderly patients compared to young patients were selected with the threshold of |L2FC| > 2 and padj ≤ 0.0001. The down-regulated gene ATF4 was chosen by GSEA analysis and ROC analysis with AUC > 0.95. We found 3059 genes with differential transcript levels (GDTLs) in AML patients of different age. Among them, 2048 genes are down-regulated and 651 genes are up-regulated in elderly patients. We found that gene transcript profiles in elderly patients is obviously different from those in young patients, including a collection of down-regulated genes related to proteins processing in endoplasmic reticulum and immunity. We further identified that genes of pathway in cancer and mitogen activated protein kinase (MAPK) pathway, involved in natural immunity and metabolism, are significantly down-regulated in elderly patients. Among all screened genes with decreased transcript levels, we believe that activating transcription factor 4 (ATF4) is a biomarker indicating different chemotherapy strategies for elderly patients. In summary, gene transcript profiles are different in platelets of elderly and young AML patients. And ATF4 can be a useful biomarker indicating different chemotherapy strategies for AML patients with different ages.

中文翻译：

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血小板转录组谱为老年急性髓细胞白血病患者提供潜在的治疗靶点

急性髓系白血病 (AML) 是成人中最常见的急性白血病，临床诊断的中位年龄为 68 岁。大约 60% 的患者年龄在 60 岁以上。AML 患者有多种治疗选择。但对于老年患者，由于遗传、分子和年龄相关因素，完全缓解率令人失望。新一代测序技术的发展使得针对不同年龄的患者寻求个体化策略成为可能。本研究首次分析了不同年龄 AML 患者血小板的转录组谱。使用 Illumina TruSeq Stranded mRNA 文库 Prep Kit 和 Illumina HiSeq4000 测序仪对 10 名老年患者和 7 名年轻患者的 AML 进行血小板 RNA 测序。随着获得的 FASTQ 测序数据，R程序分析老年人与年轻AML患者之间的统计分析。GO 和 KEGG 富集分析是通过 R 包 clusterProfiler 进行的。与年轻患者相比，老年患者中下调/上调的前 10 个基因以|L2FC| 为阈值进行选择。> 2 且 padj ≤ 0.0001。通过GSEA分析和ROC分析选择下调基因ATF4，AUC>0.95。我们在不同年龄的 AML 患者中发现了 3059 个具有差异转录水平 (GDTL) 的基因。其中，老年患者有2048个基因下调，651个基因上调。我们发现老年患者的基因转录谱与年轻患者明显不同，包括一系列与内质网蛋白质加工和免疫相关的下调基因。我们进一步发现癌症通路基因和参与自然免疫和代谢的丝裂原活化蛋白激酶（MAPK）通路基因在老年患者中显着下调。在所有筛选出的转录水平降低的基因中，我们认为激活转录因子 4 (ATF4) 是一种生物标志物，表明对老年患者采取不同的化疗策略。总之，老年和年轻 AML 患者的血小板中的基因转录谱是不同的。ATF4 可以作为一种有用的生物标志物，指示不同年龄 AML 患者的不同化疗策略。在所有筛选出的转录水平降低的基因中，我们认为激活转录因子 4 (ATF4) 是一种生物标志物，表明对老年患者采取不同的化疗策略。总之，老年和年轻 AML 患者的血小板中的基因转录谱是不同的。ATF4 可以作为一种有用的生物标志物，指示不同年龄 AML 患者的不同化疗策略。在所有筛选出的转录水平降低的基因中，我们认为激活转录因子 4 (ATF4) 是一种生物标志物，表明对老年患者采取不同的化疗策略。总之，老年和年轻 AML 患者的血小板中的基因转录谱是不同的。ATF4 可以作为一种有用的生物标志物，指示不同年龄 AML 患者的不同化疗策略。