Comprehensive analysis of the RSK gene family in acute myeloid leukemia determines a prognostic signature for the prediction of clinical prognosis and treatment responses

Hematology. 2023 Dec;28(1):2235833. doi: 10.1080/16078454.2023.2235833.

Abstract

Objective: The prognosis of acute myeloid leukemia (AML) remains poor although the basic and translational research has been highly productive in understanding the genetics and pathopoiesis of AML and a plethora of targeted therapies have been developed. Consequently, it is crucial to deepen the knowledge of molecular pathogenesis underlying AML for the advancement of new treatment options.

Method: A RSK gene family-related signature was constructed to investigate whether RSK gene family members were useful in predicting the prognosis of AML patients. The relationship between the RSK gene family-related signature and the infiltration of immune cells was further assessed using the CIBERSORT algorithm. The 'oncoPredict' package was used to analyze relationships between the RSK gene family-related signature and the sensitivity to drugs or small molecules.

Results: Patients were classified into two groups using the RSK gene family-related signature following the median risk score. Overall survival (OS) was significantly longer in patients with low-risk scores than that in patients with high-risk scores as showed by both training and validation datasets. Moreover, the signature was helpful in predicting 1-year, 3-year, and 5-year OS in training and validation datasets. In addition, it was identified that low-risk patients exhibited greater sensitivity to 20 drugs or small molecules and that high-risk patients had higher sensitivity to 38 drugs or small molecules.

Conclusion: RSK gene family members, particularly RPS6KA1 and RPS6KA4, may help to predict prognosis for AML patients. Furthermore, RPS6KA1 may serve as a novel drug target for AML.

Keywords: Acute myeloid leukemia; RPS6KA1; RPS6KA4; RSK gene family; prognosis; prognostic signature; treatment response.

MeSH terms

  • Algorithms
  • Family*
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Prognosis
  • Ribosomal Protein S6 Kinases* / genetics

Substances

  • Ribosomal Protein S6 Kinases
  • RPS6KA1 protein, human
  • RPS6KA4 protein, human