Defective Sphingolipids Metabolism and Tumor Associated Macrophages as the Possible Links Between Gaucher Disease and Blood Cancer Development
Abstract
:1. Introduction
2. Gaucher Disease
3. Cancers Frequency/Incidence in Gaucher Disease
4. Pathogenesis of Cancer Associated with GD
4.1. Sphingolipids
4.2. Deficiency of Acid β-Glucosidase, Immune Pathology in Gaucher Disease
4.3. Lipid Rafts (Detergent-Resistant Membranes, DRM)
4.4. Chitotriosidase
4.5. Tumor Associated Macrophages (TAM)
5. What Induces Cancerogenesis in GD?
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
C1P | ceramid-1-phosphate |
CAPK | ceramide-activated protein kinase |
ERT | enzyme replacement therapy |
GCs | Gaucher cells |
GD | Gaucher disease |
GlcCer | glucosyloceramide |
MCP-1 | monocyte chemoattractant protein 1, known also as CCL2 |
MGUS | monoclonal gammopathy of undetermined significance |
MM | multiple myeolma |
S1P | sphingosine-1-phosphate |
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Pathophysiology of Gaucher Disease | ||
---|---|---|
Gene expression error | Biallelic mutation GBA1 gene (glucocerebrosidase 1 gene) | Biallelic mutation of the PSAP gene (prosaposine prekursor gene) |
Consequence of gene mutation | Lysosomal deficiency of glucocerebrosiadase | Saposin C deficiency SAP = sphingolipid activator |
Glucocerebrosidase activity | No activation of glucocerebrosidase | No activation of glucocerebrosidase |
Accumulation of glucosylceramide | Within the organelles, late endosomes and lysosomes | Within the organelles, late endosomes and lysosomes |
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Wątek, M.; Piktel, E.; Wollny, T.; Durnaś, B.; Fiedoruk, K.; Lech-Marańda, E.; Bucki, R. Defective Sphingolipids Metabolism and Tumor Associated Macrophages as the Possible Links Between Gaucher Disease and Blood Cancer Development. Int. J. Mol. Sci. 2019, 20, 843. https://doi.org/10.3390/ijms20040843
Wątek M, Piktel E, Wollny T, Durnaś B, Fiedoruk K, Lech-Marańda E, Bucki R. Defective Sphingolipids Metabolism and Tumor Associated Macrophages as the Possible Links Between Gaucher Disease and Blood Cancer Development. International Journal of Molecular Sciences. 2019; 20(4):843. https://doi.org/10.3390/ijms20040843
Chicago/Turabian StyleWątek, Marzena, Ewelina Piktel, Tomasz Wollny, Bonita Durnaś, Krzysztof Fiedoruk, Ewa Lech-Marańda, and Robert Bucki. 2019. "Defective Sphingolipids Metabolism and Tumor Associated Macrophages as the Possible Links Between Gaucher Disease and Blood Cancer Development" International Journal of Molecular Sciences 20, no. 4: 843. https://doi.org/10.3390/ijms20040843