CD34, also known as Cluster of Differentiation 34, is a transmembrane phosphoglycoprotein that is primarily known for being a surface marker for hematopoietic stem cells (HSCs) and progenitor cells (1,2). The CD34 protein consists of a heavily glycosylated extracellular domain, a single-pass transmembrane helix, and a cytoplasmic tail with PDZ binding motifs (1,3). Human CD34 has two protein isoforms consisting of 385 amino acids (aa) for the canonical isoform and 328 aa for isoform 2 (3,4). The canonical CD34 isoform has calculated theoretical molecular weight of 40 kDa and an observed molecular weight of ~115 kDa (1,3,4). L-Selectin (CD62L) is the most common ligand for CD34, but it has also been shown to bind CrkL (1,3).
CD34 has commonly been used as a marker for the diagnosis and classification of various diseases and pathologies including leukemia and solitary fibrous tumor (SFT) (2,5). In terms of immunohistochemistry and histopathology, CD34 has been the most common marker for SFT and is expressed in ~79% of cases (5). In addition to its use as a cell marker, CD34-postive (CD34+) hematopoietic stem cells have been used therapeutically in patients following radiation or chemotherapy due to their regenerative potential (6). There are several clinical trials showing promising results for CD34+ cell therapy for cardiovascular diseases including heart failure, ischemia, dilated cardiomyopathy, acute myocardial infarction, and angina (6). Besides hematopoietic lineages, CD34 is also expressed in non-hematopoietic cells including mesenchymal stem cells, endothelial cells and progenitors, fibrocytes, muscle satellite cells, and some cancer stem cells (1,3). While the clinical and cell therapy applications of CD34 as a cell marker is well documented, the function of CD34 is less understood but has been implicated in many cellular processes such as adhesion, proliferation, signal transduction, differentiation, and progenitor phenotype maintenance (1,3).
1. Sidney, L. E., Branch, M. J., Dunphy, S. E., Dua, H. S., & Hopkinson, A. (2014). Concise review: evidence for CD34 as a common marker for diverse progenitors. Stem cells (Dayton, Ohio), 32(6), 1380-1389. https://doi.org/10.1002/stem.1661
2. Krause, D. S., Fackler, M. J., Civin, C. I., & May, W. S. (1996). CD34: structure, biology, and clinical utility. Blood, 87(1), 1-13
3. Kapoor, S., Shenoy, S. P., & Bose, B. (2020). CD34 cells in somatic, regenerative and cancer stem cells: Developmental biology, cell therapy, and omics big data perspective. Journal of cellular biochemistry, 121(5-6), 3058-3069. https://doi.org/10.1002/jcb.29571
4. Uniprot (P28906)
5. Davanzo, B., Emerson, R. E., Lisy, M., Koniaris, L. G., & Kays, J. K. (2018). Solitary fibrous tumor. Translational gastroenterology and hepatology, 3, 94. https://doi.org/10.21037/tgh.2018.11.02
6. Prasad, M., Corban, M. T., Henry, T. D., Dietz, A. B., Lerman, L. O., & Lerman, A. (2020). Promise of autologous CD34+ stem/progenitor cell therapy for treatment of cardiovascular disease. Cardiovascular research, 116(8), 1424-1433. https://doi.org/10.1093/cvr/cvaa027