Table 1.
Cytokines and growth factors differentially expressed in MDS
| Cytokine/factor | Levels | Tissue | Plasma/cell type | Associations | References |
|---|---|---|---|---|---|
| GM-CSF | Normal/low | PB, BM | Plasma | Shetty et al.17 | |
| EGF | Low | PB | Plasma | Feng et al.31 | |
| CXCL5 | Low | PB | Plasma | Feng et al.31 | |
| IL-10 | Low | PB | Plasma | Kornblau et al.30 | |
| CCL5 | Low | PB | Plasma | Pardanani et al.32 | |
| M-CSF | High | BM | Mononuclears | Allampallam et al.18 | |
| G-CSF | High | PB | Plasma | Direct: BM cellularity | Kornblau et al.,30 Feng et al.,31 Pardanani et al.32 |
| TNF-α | High | BM, PB | Whole BM aspirates, BM plasma, BMMC cultures, fibroblast cultures, macrophage cultures, PB plasma | Direct: macrophage count, rate of BM apoptosis, FAB subtypesa, WHO stratification, fatigue; reverse: Hb levels, patient survival | Shetty et al.,17 Allampallam et al.,18 Kitagawa et al.,19 Deeg et al.,20 Flores-Figueroa et al.,21 Gersuk et al.,22 Sawanbori et al.,23 Tsimberidou et al.,28 Meyers et al.,29 Feng et al.,31 Pardanani et al.32 |
| IFN-γ | Higha | BM, PB | Whole BM aspirates, mainly in myeloid cells | Kitagawa et al.,19 Pardanani et al.32 | |
| TGF-β | Higha | BM | Whole BM aspirates | Shetty et al.,17 Qadir et al.25 | |
| IL-1α/1βR | Higha | BM, PB | Mononuclears, parenchyma, PB plasma | Direct: fatigue | Allampallam et al.,18 Meyers et al.,29 Kornblau et al.,30 Feng et al.,31 Pardanani et al.32 |
| IL-1RAP | High | BM | Stem and progenitor cells | IPSS risk (high) | Barreyro et al.60 |
| IL-4 | Higha | PB | Plasma | Pardanani et al.32 | |
| IL-6 | Higha | BM, PB | Plasma, BMMC cultures, fibroblast cultures | Direct: fatigue; reverse: survival | Flores-Figueroa et al.,21 Hsu et al.,24 Meyers et al.,29 Feng et al.,31 Pardanani et al.32 |
| IL-7 | High | PB | Plasma | Reverse: survival | Pardanani et al.32 |
| IL-8 | Higha | BM, PB | Plasma | Direct: WHO stratification, IPSS risk | Hsu et al.,24 Kornblau et al.,30 Pardanani et al.32 |
| IL-12 | High | PB | Plasma | Kornblau et al.30 | |
| IL-13 | High | PB | Plasma | Pardanani et al.32 | |
| IL-15 | High | PB | Plasma | Kornblau et al.,30 Pardanani et al.32 | |
| IL-17 | High | PB | Plasma | Kordasti et al.33 | |
| VEGF | High | BM, PB | PB serum, whole BM aspirates | Brunner et al.,26 Verstovsek et al.,27 Pardanani et al.32 | |
| ANG | High | PB | Plasma | Brunner et al.26 | |
| CXCL10 | Higha | PB | Plasma | Direct: circulating blasts, thrombocytopenia; reverse: survival | Kornblau et al.,30 Pardanani et al.32 |
| CCL3 | High | PB | Plasma | Feng et al.31 | |
| CCL4 | High | PB | Plasma | Feng et al.31 | |
| HGF | High | PB | Plasma | Feng et al.,31 Pardanani et al.32 | |
| MIP-1β | High | PB | Plasma | Pardanani et al.32 | |
| MIG | High | PB | Plasma | Pardanani et al.32 | |
| Eotaxin | High | PB | Plasma | Pardanani et al.32 | |
| MCP-1 | High | PB | Plasma | Pardanani et al.32 |
Abbreviations: ANG, angiogenin; BM, bone marrow; CCL, C-C motif ligand; CXCL, C-X-C motif ligand; EGF, epidermal growth factor; FAB, French-American-British classification; HGF, hepatocyte growth factor; PB, perpheral blood; G-CSF, granulocyte colony-stimulating factor; Hb, hemoglobin; IFN-γ, interferon gamma; IL-1RAP, interleukin-1R accessory protein; MCP, monocyte chemotactic protein 1; MDS, myelodysplastic syndrome; MIG, monokine induced by interferon γ; MIP-1β, macrophage inflammatory protein; M-CSF, macrophage colony-stimulating factor; TGF-β, transforming growth factor beta; VEGF, vascular endothelium growth factor; WHO, World Health Organization.
Discrepancies exist among different studies: one work reported IFN-γ, IL-4 and IL-6 to be downregulated and IL-1 to be expressed at normal levels;30 the direct association of TNF-α with FAB subtypes was not confirmed by some groups;21,30 no differences were found in IL-8 and CXCL10 levels in one study.31