CD123: A Novel Biomarker for Diagnosis and Treatment of Leukemia

摘要

Leukemia is a group of progressive hematologic malignancies derived from stem cells in bone marrow which causes a large number of cancer deaths. Even with treatment such as traditional chemotherapy, targeted therapy, and allogeneic stem cell transplantation (allo-HSCT), many patients suffer from relapse/refractory disease, and the overall survival is dismal. Leukemic stem cells (LSCs) are induced by gene mutations and undergo an aberrant and poorly regulated proliferation process which is involved in the evolution, relapse, and drug-resistance of leukemia. Emerging studies demonstrate that CD 123, the interleukin 3 receptor alpha (IL-3Ra), is highly expressed in LSCs, while not normal hematopoietic stem cells (HSCs), and associates with treatment response, minimal residual disease (MRD) detection and prognosis. Furthermore, CD 123 is an important marker for the identification and targeting of LSCs for refractory or relapsed leukemia. Anti-CD 123 target-therapies in pre-clinical studies and clinical trials confirm the utility of anti-CD 123 neutralizing antibody-drugs, CD3xCD123 bispecific antibodies, dual-affinity retargeting (DART), and anti-CD 123 chimeric antigen receptor-modified T-cell (CAR-T) therapies in progress. This review summarizes the most recent progress on the study of CD 123 biology and the development of novel CD 123-targeted therapies.