Related Experiment Video
Updated: May 30, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated
Fabio P S Santos1, Hagop Kantarjian, David McConkey
1Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Background:
Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma (MM) and mantle-cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown.
Methods:
We conducted a pilot trial to evaluate the activity of single-agent bortezomib in CML. Seven patients with imatinib-refractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11 every 3 weeks.
Results:
The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients experienced grade 3/4 nonhematologic toxicities.
Conclusion:
Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to using proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors (TKIs) or as a strategy to eradicate leukemic stem cells.
Insights
Bortezomib showed minimal efficacy and significant toxicity in patients with imatinib-refractory chronic myeloid leukemia (CML). Further research into combination therapies or stem cell eradication strategies is recommended for CML treatment.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Proteasome inhibitors, like bortezomib, induce cancer cell apoptosis.
- Bortezomib is approved for multiple myeloma and mantle-cell lymphoma.
- Bortezomib's efficacy in imatinib-resistant chronic myeloid leukemia (CML) was previously unknown.
Purpose of the Study:
- To evaluate the activity of single-agent bortezomib in patients with CML.
- To assess the safety and efficacy of bortezomib in imatinib-refractory CML.
Main Methods:
- A pilot trial was conducted.
- Seven patients with imatinib-refractory CML received bortezomib (1.5 mg/m2) on specific days over 3-week cycles.
Main Results:
- No patient achieved hematologic or cytogenetic response.
- Bortezomib therapy resulted in a temporary decrease in basophil counts in three patients.
- Six patients experienced severe nonhematologic toxicities (grade 3/4).
Conclusions:
- Bortezomib demonstrated limited efficacy and substantial toxicity in imatinib-refractory CML.
- Future CML treatment strategies should explore proteasome inhibitors in combination with tyrosine kinase inhibitors (TKIs).
- Investigating bortezomib for leukemic stem cell eradication in CML is warranted.
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers