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

BMC Cancer. 2021 Dec 14;21(1):1331. doi: 10.1186/s12885-021-09076-w.

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 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.

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: Acute lymphoblastic leukemia; Ferroptosis; Immune; Sorafenib; Unsupervised clustering.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Apoptosis
  • Child
  • Cluster Analysis
  • Female
  • Ferroptosis / genetics*
  • Ferroptosis / immunology
  • Humans
  • Leukemia, B-Cell / drug therapy
  • Leukemia, B-Cell / genetics*
  • Leukemia, B-Cell / immunology*
  • Male
  • Middle Aged
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Prognosis
  • RNA-Seq
  • Risk Factors
  • Sorafenib / therapeutic use
  • Treatment Outcome
  • Tumor Microenvironment / immunology
  • Unsupervised Machine Learning
  • Young Adult

Substances

  • Antineoplastic Agents
  • Sorafenib