Identification of immune subtypes of Ph-neg B-ALL with ferroptosis related genes and the potential implementation of Sorafenib.

Identification of immune subtypes of Ph-neg B-ALL with ferroptosis related genes and the potential implementation of Sorafenib.
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铁死亡相关基因 Ph-neg B-ALL 免疫亚型的鉴定及索拉非尼的潜在应用

DOI:
10.1186/s12885-021-09076-w
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发表时间:
2021-12-14
期刊:
影响因子:
3.8
通讯作者:
Sun A
Sun A
中科院分区:
医学2区
文献类型:
--
作者:
Hong Y;Zhang L;Tian X;Xiang X;Yu Y;Zeng Z;Cao Y;Chen S;Sun A

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费城染色体阴性B细胞急性淋巴细胞白血病(Ph-neg B-ALL)由于缺乏靶向治疗和白血病的异质性,临床治疗后的结局因人而异。铁凋亡是最近发现的与癌症密切相关的程序性细胞死亡。然而,很少有相关研究报道其在急性淋巴细胞白血病中的意义。在此,我们收集了在我们中心诊断的80例Ph-neg B-ALL患者的临床数据,并对其初始骨髓液样本进行了RNA-seq。通过对24个铁凋亡相关基因(FRG)的无监督机器学习K-means聚类,将聚类的患者分为3个变异风险组,并进行生物信息学分析。结果,我们发现了免疫微环境和基因组差异的显著异质性。此外,还在我们的队列中分析了免疫检查点抑制剂应答和索拉非尼在Ph阴性B-ALL中的潜在应用。最后,建立了一个基于8个FRG的预后模型,用于评估Ph阴性B-ALL患者的风险。同时,我们的研究证明了铁凋亡在Ph-neg B-ALL中的关键作用,索拉非尼可能会改善高危Ph-neg B-ALL患者的生存率。在线版本包含补充材料,可通过10.1186/s12885 - 021 - 09076-w获得。
The clinical outcome of Philadelphia chromosome-negative B cell acute lymphoblastic leukemia (Ph-neg B-ALL) varies considerably from one person to another after clinical treatment due to lack of targeted therapies and leukemia’s heterogeneity. Ferroptosis is a recently discovered programmed cell death strongly correlated with cancers. Nevertheless, few related studies have reported its significance in acute lymphoblastic leukemia. Herein, we collected clinical data of 80 Ph-neg B-ALL patients diagnosed in our center and performed RNA-seq with their initial bone marrow fluid samples. Throughout unsupervised machine learning K-means clustering with 24 ferroptosis related genes (FRGs), the clustered patients were parted into three variant risk groups and were performed with bioinformatics analysis. As a result, we discovered significant heterogeneity of both immune microenvironment and genomic variance. Furthermore, the immune check point inhibitors response and potential implementation of Sorafenib in Ph-neg B-ALL was also analyzed in our cohort. Lastly, one prognostic model based on 8 FRGs was developed to evaluate the risk of Ph-neg B-ALL patients. Jointly, our study proved the crucial role of ferroptosis in Ph-neg B-ALL and Sorafenib is likely to improve the survival of high-risk Ph-neg B-ALL patients. The online version contains supplementary material available at 10.1186/s12885-021-09076-w.
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