Interleukin-3 receptor subunit alpha (CD123) and C-type lectin domain family 12 member A (CLL-1) (CD123 and CLL-1)

CD123 (Interleukin-3 receptor subunit alpha) and CLL-1 (C-type lectin-like molecule-1) are two prominent surface antigens frequently co-expressed on the surface of acute myeloid leukemia (AML) blasts and leukemic stem cells (LSCs) (Source: UniProt P26951, Q5QGZ9). CD123 is the alpha subunit of the IL-3 receptor and plays a critical role in regulating hematopoiesis and cell proliferation; however, its expression on normal hematopoietic stem cells (HSCs) can lead to off-target myelotoxicity when targeted alone (Source: PubMed 28811300). CLL-1, also known as CLEC12A, is a type II transmembrane glycoprotein involved in the negative regulation of inflammation and is notably absent on healthy HSCs, making it a highly specific marker for AML (Source: PubMed 31533927). The dual targeting of CD123 and CLL-1 is an emerging therapeutic strategy designed to enhance the eradication of LSCs while minimizing damage to the healthy bone marrow compartment. This approach is primarily being explored through the development of bispecific antibodies and dual-targeted CAR-T cell therapies to overcome antigen escape and improve clinical outcomes in refractory or relapsed AML patients (Source: PubMed 33106340).

Other names

IL3RACLEC12AMICLC-type lectin-like molecule-1Interleukin-3 receptor alpha chainKLRL1

Dual-targeting of leukemic blasts and leukemic stem cells (LSCs) via antibody-drug conjugates, bispecific antibodies, or chimeric antigen receptor (CAR) T-cells to induce apoptosis, antibody-dependent cellular cytotoxicity (ADCC), and direct T-cell mediated lysis.