Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy
Mrinal M Patnaik1, Tariq I Mughal2,3, Christopher Brooks3
1Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Abstract:
Following the observation of interleukin 3 receptor α chain (IL-3Rα; CD123) upregulation on leukemia stem cells (LSCs) almost two decades ago, targeted treatment via CD123-diptheria toxin conjugates has now been tested in patients with diverse myeloid malignancies. Targeted eradication of LSCs could result in effective treatments for many challenging diseases initiated by these cells. Consequently, considerable effort has been directed toward targeting CD123 as a potential strategy for treating patients with hematologic malignancies in which CD123 is overexpressed. However, these therapies have had limited success so far, highlighting the need for suitable criteria to identify patients who could benefit from them. Given the diversity in CD123 expression across different hematologic malignancies, understanding CD123 expression patterns and the functional pathogenetic significance is crucial. Here, we review the methodologies available for CD123 assessment and discuss the biological and clinical characteristics of patients for whom CD123-targeting therapies may have a clinical impact.
Insights
Targeting interleukin 3 receptor α chain (IL-3Rα; CD123) on leukemia stem cells (LSCs) shows promise for myeloid malignancies. Identifying patients who benefit from CD123-targeted therapies requires understanding expression patterns and clinical impact.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Interleukin 3 receptor α chain (IL-3Rα; CD123) is upregulated on leukemia stem cells (LSCs).
- Targeted therapies using CD123-diphtheria toxin conjugates have been investigated for myeloid malignancies.
- Limited success of current CD123-targeted therapies necessitates better patient selection criteria.
Purpose of the Study:
- To review methodologies for assessing CD123 expression.
- To discuss biological and clinical characteristics of patients who may benefit from CD123-targeting therapies.
- To understand CD123 expression patterns and their pathogenetic significance in hematologic malignancies.
Main Methods:
- Review of existing literature on CD123 assessment methodologies.
- Analysis of biological and clinical data related to CD123 expression in hematologic malignancies.
- Discussion of the functional significance of CD123 in disease pathogenesis.
Main Results:
- CD123 expression varies across different hematologic malignancies.
- Understanding CD123 expression patterns is crucial for effective targeted therapy.
- Patient selection criteria are needed to optimize CD123-targeted treatment outcomes.
Conclusions:
- CD123-targeted therapies offer a potential strategy for treating hematologic malignancies.
- Further research is needed to refine patient selection for CD123-targeted treatments.
- Comprehensive understanding of CD123 biology and expression is key to clinical success.
