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Updated: Aug 14, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
An acute lymphoblastic leukemia cell-based preclinical assay revealed functional differences between commercial
Diego Fernando Rincón Reyes1, José Luis Padilla Agudelo1, Andrea Isabel Pinilla da Silva1
1Immunology and Molecular Epidemiology Research Group (GIEM), Escuela de Microbiología, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia.
Background:
L-asparaginase (L-ASNase) is an essential component of chemotherapy strategies due to its differential action between normal and leukemic cells. Recently, concerns about the efficiency of commercial formulations administered in developing countries have been reported, and available methods have limitations for directly determining the quality of the formulation of the medications.
Procedure:
We developed a cell-based protocol to analyze the activity of different L-ASNase formulations used in Colombia to induce apoptosis of the NALM-6 cell line after 24, 48, and 72 hours, using flow cytometry. Then we compared results and determined the statistically significant differences.
Results:
Three statistically different groups, ranging from full to no activity against leukemic cells, using 0.05, 0.5, and 5.0 IU/ml concentrations, were identified. Group 1 (asparaginase codified [ASA]2-4) exhibited very low to no activity against B-cell acute lymphoblastic leukemia (B-ALL) cells. Group 2 (ASA6) exhibited intermediate-level activity, and group 3 (ASA1 and ASA5) exhibited high activity.
Conclusions:
Differences found between the therapeutic formulations of L-ASNase distributed in Colombia raise concerns about the quality of the treatment administered to patients in low- and middle-income countries. Therefore, we recommend a preclinical evaluation of formulations of L-ASNase in order to prevent therapeutical impacts on the outcome of ALL patients.
