Abstract
Simple SummaryCD123 is overexpressed in multiple hematologic malignancies. Advances in CD123-targeted therapies over the past decade have positioned this molecule as an integral biomarker in current practice. This review provides an overview of CD123 biology and in-depth discussion of clinical laboratory techniques used to determine CD123 expression in various hematolymphoid neoplasms. In addition, we describe various pharmacologic strategies and agents that are available or under evaluation for targeting CD123.CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated in leukemic stem cells relative to non-neoplastic hematopoietic stem cells, which makes it a useful diagnostic and therapeutic biomarker in hematologic malignancies. Varying levels of evidence have shown that CD123-targeted therapy represents a promising therapeutic approach in several cancers. Tagraxofusp, an anti-CD123 antibody conjugated to a diphtheria toxin, has been approved for use in patients with blastic plasmacytoid dendritic cell neoplasm. Multiple clinical trials are investigating the use of various CD123-targeting agents, including chimeric antigen receptor-modified T cells (expressing CD123, monoclonal antibodies, combined CD3-CD123 dual-affinity retargeting antibody therapy, recombinant fusion proteins, and CD123-engager T cells. In this review, we provide an overview of laboratory techniques used to evaluate and monitor CD123 expression, describe the strengths and limitations of detecting this biomarker in guiding therapy decisions, and provide an overview of the pharmacologic principles and strategies used in CD123-targeted therapies.
Highlights
CD123 has emerged in recent years as an attractive novel target of therapy
CD123 expression has been demonstrated on neoplastic cells in blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), acute lymphoblastic leukemia/lymphoma (ALL), hairy cell leukemia (HCL), systemic mastocytosis (SM), etc. [1,5]
We provide an overview of CD123 biology, discuss current clinical laboratory techniques used to evaluate CD123 expression on neoplastic cells and salient features of CD123 expression in various hematolymphoid neoplasms, and discuss the major classes of targeted
Summary
CD123 has emerged in recent years as an attractive novel target of therapy. CD123 is normally expressed on hematopoietic stem cells (HSC) [1]. Cellular therapy approaches using CD123-targeting chimeric antigen receptor (CAR) T cells have emerged as another exciting approach [6,7]. As these therapies require knowledge of the expression status of CD123 at baseline and during the course of treatment, clinical laboratory techniques for measuring CD123 expression as a biomarker of therapy have gained unprecedented urgency. We provide an overview of CD123 biology, discuss current clinical laboratory techniques used to evaluate CD123 expression on neoplastic cells and salient features of CD123 expression in various hematolymphoid neoplasms, and discuss the major classes of targeted.
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