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The clinical outcome of Philadelphia chromosome-negative B cell acute lymphoblastic leukemia (Phneg B-ALL) varies considerably from one person to another after clinical treatment due to lack of targeted therapies and leukemia’s heterogeneity. | Hong et al. BMC Cancer 2021 21 1331 https doi.org 10.1186 s12885-021-09076-w RESEARCH ARTICLE Open Access Identification of immune subtypes of Ph- neg B-ALL with ferroptosis related genes and the potential implementation of Sorafenib Yang Hong1 2 Ling Zhang1 2 Xiaopeng Tian1 2 Xin Xiang1 2 Yan Yu1 2 Zhao Zeng1 2 Yaqing Cao1 2 Suning Chen1 2 and Aining Sun1 2 Abstract Background 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. Methods 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. Results As a result we discovered significant heterogeneity of both immune microenvironment and genomic vari- ance. 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. Conclusion 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. Keywords Ferroptosis Acute lymphoblastic leukemia Unsupervised clustering Sorafenib Immune Background 50 of B-ALL patients were negative in Philadelphia B cell acute lymphoblastic leukemia B-ALL diagnosis chromosome screening 2 and the prognosis of Phila- and treatment had
