High-throughput cell viability assessment using a luminescent ATP detection assay

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Chronic myelomonocytic leukemia (CMML) is an aggressive hematologic malignancy.
• Current standard therapies lack the ability to eradicate leukemic clones or modify disease outcomes.
• There are no approved targeted therapies for CMML, highlighting a significant therapeutic gap.

Purpose of the Study:

• To identify genotype-dependent therapeutic vulnerabilities in CMML.
• To leverage a drug repurposing strategy for rapid clinical translation of pre-approved compounds.
• To address the unmet therapeutic needs in CMML treatment.

Main Methods:

• Conducted a high-throughput chemical drug screen using a robotized platform.
• Utilized four genetically engineered hematopoietic murine cell lines modeling recurrent CMML mutations.
• Assessed cell viability using the CellTiter-Glo® luminescent cell viability assay over 48 hours.

Main Results:

• Identified potential drug candidates through a genotype-dependent screening approach.
• Demonstrated the feasibility of a drug repurposing strategy for CMML.
• The CellTiter-Glo® assay proved accurate and efficient for high-throughput screening.

Conclusions:

• High-throughput drug screening can identify novel therapeutic vulnerabilities in CMML.
• Drug repurposing offers a promising avenue for developing targeted CMML therapies.
• The described screening method is reliable, time-efficient, and adaptable for various research contexts.