Proteomic Profiling of Bone Marrow Aspirates from Patients with Methotrexate- and Vincristine-Resistant B-Cell Acute Lymphoblastic Leukemia: A Retrospective Analysis.
This retrospective proteomic analysis of treatment-naive bone marrow aspirates from pediatric B-ALL patients reports distinct protein profiles in vincristine- and methotrexate-based induction nonresponders, including consistent overexpression of TYMP and GSN.
Open original publication →What the AI sees
This retrospective proteomic analysis of treatment-naive bone marrow aspirates from pediatric B-ALL patients reports distinct protein profiles in vincristine- and methotrexate-based induction nonresponders, including consistent overexpression of TYMP and GSN.
Research significance
The reported evidence supports TYMP and GSN as candidate biomarkers associated with intrinsic nonresponse; it remains an untested inference that these proteins or their linked nucleotide-metabolism and cytoskeletal pathways could enable treatment selection or serve as therapeutic targets.
Source abstract
Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most frequent malignancy of childhood; worldwide, 487,294 new cases and 305,405 deaths were reported in 2022, including more than 5000 new cases in Mexico. Chemotherapy, delivered in induction, consolidation and maintenance phases, remains the mainstay of treatment, yet 10-20% of patients relapse after induction because of chemoresistance, whose molecular basis is still incompletely understood. Methods: This retrospective study aimed to identify proteins associated with resistance to vincristine (VCR) and methotrexate (MTX) administered during the induction phase, using LC-MS/MS proteomics and bioinformatic analysis of treatment-naive bone marrow aspirates from responders and nonresponders. Results: Nonresponders showed a distinct proteomic profile, with deregulated processes converging on cytoskeletal structure and dynamics, nucleic acid metabolism, DNA repair and RNA processing. Within these processes, thymidine phosphorylase (TYMP) and gelsolin (GSN) emerged as differentially expressed proteins, both consistently overexpressed in nonresponders at the individual-patient level. Conclusions: We conclude that cytoskeletal remodeling and nucleotide metabolism are prominent features of intrinsic chemoresistance in pediatric B-ALL, and that TYMP and GSN represent candidate biomarkers of nonresponse to VCR- and MTX-based induction that warrant validation by orthogonal methods in independent, adequately powered cohorts.