Table 1.
Non-comprehensive list of human markers that can be found on LSC and their (potential) expression on the cell surface of other healthy blood cells. Highlighted in grey are the markers expressed on the cell surface of LSC from both CD34-expressing and non-expressing acute myeloid leukemia (AML). In white: markers only demonstrated to play roles in LSC from CD34 expressing AML. N.D: Not described/MPP: multipotential progenitor/MEP: megakaryocyte–erythroid progenitor).
| Antigen | Percentage of AML Patients Expressing the Marker | Expression on Non-LSC | Expression on HSC | Expression on Other Healthy Blood Cells | Function in Healthy Conditions | References |
|---|---|---|---|---|---|---|
| CLL-1 | 92 | Yes | No | Monocytes, granulocytes, CMP, GMP | Modulates the activation state of cells during inflammation processes | Bakker et al. 2004 [57] Jiang et al. 2018 [58] Daga et al. 2019 [55] Marshall et al. 2006 [29] |
| CD9 | 40 | Yes | No | Monocytes, macrophages, granulocytes, DC, endothelial cells, B, T, and NK cells | Cell migration, adhesion, activation, | Brosseau et al. 2018 [59] Touzet et al. 2019 [47] Paprocka et al. 2017 [46] |
| CD25 | 10–25 | Yes | No | T cells and regulatory T cells | Important role for T cells survival | Saito et al. 2010 [60] Kageyama et al. 2018 [61] Triplett et al. 2012 [31] |
| CD26 | N.D | Yes | No | T, B, NK, and myeloid cells | T cell activation and proliferation, cell adhesion, metabolism | Herrmann et al. 2020 [25] Klemann et al. 2016 [62] |
| CD32 | 35 | Yes | No | Monocytes, B and T cells | Immune cell activation | Saito et al. 2010 [60] Anania et al. 2019 [30] |
| CD33 | 88 | Yes | Yes | Myeloid cells, lymphocytes, NK cells, MPP, GMP, MEP | Modulates inflammatory and immune responses by reducing tyrosine kinase dependent pathways | Ehninger et al. 2014 [63] Liu et al. 2007 [64] Laszlo et al. 2014 [65] Haubner et al. 2017 [24] |
| CD34 | 70 | Yes | Yes | Mast cells, eosinophils, neurons, fibrocytes | Regulates cell differentiation, adhesion, trafficking and proliferation | Quek et al. 2016 [36] Engelhardt et al. 2002 [16] Nielsen et al. 2008 [17] |
| CD36 | N.D | Yes | No | Platelets, monocytes, adipocytes | Fatty acid uptake, angiogenesis, PRR recognition | Silverstein et al. 2009 [66] Sachs et al. 2020 [67] Herrmann et al. 2020 [25] |
| CD38 | 5–55 (FAB subtypes) |
Yes | No | T and B cells, monocytes, NK, granulocytes, platelets, red blood cells | Regulates calcium levels and NAD+ homeostasis | Hogan et al. 2019 [38] Sarry et al. 2011 [35] Goardon et al. 2011 [40] Keyhani et al. 2000 [68] |
| CD44 | N.D | Yes | Yes | T cells, mesenchymal cells, ectodermal cells, neuron-like cells | Cell adhesion molecule, cellular signaling | Ponta et al. 2003 [69] Jin et al. 2006 [70] Bendall et al. 2000 [71] Herrmann et al. 2020 [25] |
| CD45RA | N.D | Yes | Yes | T and B cells | CD45 isoform, cell signaling | Kersten et al. 2016 [39] Goardon et al. 2011 [40] Sarry et al. 2011 [35] Holmes 2006 [41] |
| CD47 | N.D | Yes | Yes | Various healthy cells | “don’t eat me” signal on cells in order to prevent inappropriate phagocytosis | Majeti et al. 2009 [34] Jaiswal et al. 2009 [33] Sick et al. 2012 [72] |
| CD56 | Up to 20 | Yes | No | DC, T and NK cells | Linked to NK cytotoxicity | Van Acker et al. 2017 [73] Sasca et al. 2019 [74] Herrmann et al. 2020 [25] |
| CD69 | N.D | N.D | No | T cells | T cell differentiation, tissue retention, and metabolic reprogramming | Cibrián et al. 2017 [75] Sachs et al. 2020 [67] Herrmann et al. 2020 [25] |
| CD70 | N.D | Yes | No | DC | T and B cell activation | Riether et al. 2015 [76] Riether et al. 2017 [77] Borst et al. 2005 [78] |
| CD90 | 40 (in elderly patients) | Yes | Yes | Fibroblasts, neurons, endothelial cells | Maintenance of HSC, cell adhesion, matrix adhesion | Buccisano et al. 2004 [79] Blair et al. 1997 [52] Brendel et al. 1999 [50] Kisselbach et al. 2009 [80] Craig et al. 1993 [53] |
| CD93 | N.D | N.D | No (only on CD34-HSC) | Myeloid and endothelial cells | Mechanism in innate host defense | Bohlson et al. 2008 [81] Iwasaki et al. 2015 [82] Sumide et al. 2018 [83] |
| CD96 | 27 | Yes | Only 5% | T and NK cells | Inhibits NK and T cells | Fatlawi et al. 2016 [84] Georgiev et al. 2018 [27] Hosen et al. 2007 [85] |
| CD117 | 87 | Yes | Yes | GMP | Promotes HSC growth by binding the stem cell factor | Sperling et al. 1997 [86] Geissler et al. 1991 [87] Quek et al. 2016 [36] Wells et al. 1996 [88] |
| CD123 | 97 | Yes | No | Basophils, plasmacytoid DC | Proliferation, survival, activation, and differentiation by binding respective ligand | Yu et al. 2016 [88] Guthridge et al. 1998 [32] Bras et al. 2019 [45] Haubner et al. 2019 [24] Al-Mawali et al. 2017 [44] |
| CD200 | N.D | Yes | Yes | Myeloid, T and B cells | Immunoregulatory molecule | Ngwa et al. 2019 [89] Ho et al. 2020 [90] |
| CD244 | N.D | Yes | Yes | GMP, HSPC, granulocytes, monocytes, DC, NK and T cells | Regulates NK, T, and DC activation state | Zhang et al. 2017 [91] Haubner et al. 2019 [24] Quek et al. 2016 [36] Agresta et al. 2018 [92] |
| GPR56 | N.D | No | Yes | Central nervous system, T cells | Frontal cortex development, NK inhibition, cell migration, HSC generation | Pabst et al. 2016 [93] Daga et al. 2019 [55] Kartalaei et al. 2015 [94] Huang et al. 2018 [95] |
| NKG2DL (its absence defines LSC) |
Highly variable | Yes | No | Not expressed on healthy cells | Upregulation of NG2DL on malignant or virus-infected cells resulting in their clearance by NK cells | Paczulla et al. 2019 [6] Zingoni et al. 2018 [96] |
| TIM-3 | 98 | Yes | No | T cells, monocytes, macrophages, DC, and mast cells | Homeostasis-maintaining molecule of the immune system | Jan et al. 2011 [97] Haubner et al. 2019 [24] Kikushige et al. 2010 [98] Han et al. 2013 [28] |