Related Experiment Video
Updated: Apr 13, 2026
Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance
P O Pietarinen1, T Pemovska2, M Kontro1
1Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Abstract:
Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies.
Insights
New drugs show promise for chronic myeloid leukemia in blast crisis (CML BC). High-throughput screening identified vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors as potential treatments for this challenging leukemia.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Chronic myeloid leukemia in blast crisis (CML BC) presents significant treatment challenges.
- Despite advances in tyrosine kinase inhibitor (TKI) therapy, effective treatments for CML BC remain limited.
Purpose of the Study:
- To identify novel drug candidates for CML BC using an unbiased, high-throughput drug screening platform.
- To compare drug responses in CML cell lines and primary patient samples.
Main Methods:
- Utilized three CML cell lines (K562, EM-2, MOLM-1) and primary leukemic cells from three CML BC patients.
- Drug sensitivity and resistance testing platform screened 295 anticancer agents.
- Correlated drug sensitivity scores and response profiles between cell lines and patient samples.
Main Results:
- Drug response profiles of cell lines and patient samples showed good correlation and were distinct from other leukemia types.
- CML cell lines were sensitive to TKIs, and clinically TKI-resistant patient samples exhibited ex vivo resistance.
- Identified vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors as novel candidate drugs for CML BC.
Conclusions:
- Vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors warrant further investigation in larger patient cohorts.
- These findings support the development of rational combination therapies for CML BC.
- High-throughput drug screening is effective for identifying new therapeutic strategies in CML BC.
Related Concept Videos
01:26Drug Discovery: Overview
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...