CD123
OVERVIEW
CD123 is the alpha subunit of the interleukin-3 (IL-3) receptor. IL-3 is produced by activated T lymphocytes. IL-3 together with other growth factors stimulates the development and mediates the survival of a wide range of hematopoietic cells in bone marrow.1,2,3 CD123 levels on normal hematopoietic stem cells are very low, but early common myeloid progenitors express higher CD123 levels.3,4
IMPLICATIONS IN CANCER
CD123 expression is low on normal hematopoietic stem cells and is overexpressed in multiple hematologic malignancies including AML and BPDCN.3,4 CD123 is not expressed or weakly expressed on most normal cells and therefore is a useful biomarker and therapeutic target.5,6 All cases of BPDCN are CD123 positive and detection of CD123 is required for BPDCN diagnosis.7 CD123 is overexpressed in most AML cases, correlates with mutations in NPM1 and FLT3, and is associated with negative prognosis which may be due to increased sensitivity to IL-3 binding and downregulation of CXCR4.4,8-11
- Rothenberg ME, Owen WF Jr, Silberstein DS, et al. Human eosinophils have prolonged survival, enhanced functional properties, and become hypodense when exposed to human interleukin 3. J Clin Invest. 1988;81(6):1986-92.
- Lantz CS, Boesiger J, Song CH, et al. Role of uinterleukin-3 in mast-cell and basophilk development and in immunity to parasites. Nature. 1998;392(6671):90–93.
- Testa U, Pelosi E, Frankel A. CD123 is a membrane biomarker and a therapeutic target in hematologic malignancies. Biomark Res. 2014;2(1):4.
- Jordan CT, Upchurch D, Szilvassy SJ, et al. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia. 2000;14(10):1777-1784.
- Kovtun Y, Jones GE, Adams S, et al. A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells. Blood Adv. 2018 Apr 24;2(8):848-858.
- Pemmaraju N, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019;380:1628-1637.
- Pemmaraju N, Kantarjian H, Sweet K, et al. North American Blastic Plasmacytoid Dendritic Cell Neoplasm Consortium: position on standards of care and areas of need. Blood. 2023;141(6):567-578.
- Muñoz L, Nomdedéu JF, López O, et al. Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica. 2001;86(12):1261-9.
- De Smet D, Trullemans F, Jochmans K, et al. Diagnostic potential of CD34+ cell antigen expression in myelodysplastic syndromes. Am J Clin Pathol. 2012;138(5):732-43.
- Ehninger A, Kramer M, Röllig C, et al. Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia. Blood Cancer J. 2014;4(6):e218.
- Rollins-Raval M, Pillai R, Warita K, et al. CD123 immunohistochemical expression in acute myeloid leukemia is associated with underlying FLT3-ITD and NPM1 mutations. Appl Immunohistochem Mol Morphol. 2013;21:212-17.
