Mass spectrometry proteomic profiling and treatment response in pediatric B-cell acute lymphoblastic leukemia: a pilot study

Abstract

Background

In Mexico, cancer represents the leading cause of pediatric death by disease, with over half the cases due to acute lymphoblastic leukemia (ALL). Despite the use of clinical, biochemical, immunological, and genetic variables for risk stratification, minimal residual disease (MRD) remains one of the strongest predictor of outcomes. Although Mass spectrometry-based proteomic studies are growing in the oncology field, pediatric ALL is yet to benefit from it. This pilot study aims to describe the lymphoblast's protein expression profile obtained through LC-MS/MS shotgun proteomics from four pediatric patients with treatment-naïve B-cell ALL and compare it according to their response to remission induction treatment measured by MRD.

Material and methods

Protein isolates from bone marrow were analyzed using LC-MS/MS, and differentially expressed proteins were analyzed via Ingenuity Pathway Analysis. Patients were grouped according to MRD levels (good response: <0.01, slow-suboptimal response: 0.01–0.99) at the end of induction treatment.

Results

Between 880 and 1724 proteins were identified per patient, with 631 common across all cases. Protein expression showed 36 upregulated and 63 downregulated elements in the suboptimal response group; several of these belonging to pathways that drive cell cycle activation through activation of MYC, YAP1, and SRF.

Conclusion

The proteomic characterization in these four Mexican pediatric B-ALL patients showed that the expression pattern might be more similar in those with the same type of MRD response. However a large number of subjects would be needed to draw any meaningful conclusion. In addition, MS-proteomic studies could be useful to detect proteins with clinical use as diagnostic biomarkers, and to identify drug targets in the context of precision medicine.