| Autor: |
Berk, Lieke C. J., Veer, Arian, Willemse, Marieke E., Theeuwes, Myrte J. G. A., Luijendijk, Mirjam W., Tong, Wing H., Sluis, Inge M., Pieters, Rob, Boer, Monique L. |
| Předmět: |
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| Zdroj: |
British Journal of Haematology; Jul2014, Vol. 166 Issue 2, p240-249, 10p, 1 Chart, 6 Graphs |
| Abstrakt: |
Malignant cells infiltrating the bone marrow ( BM) interfere with normal cellular behaviour of supporting cells, thereby creating a malignant niche. We found that CXCR4-receptor expression was increased in paediatric precursor B-cell acute lymphoblastic leukaemia ( BCP- ALL) cells compared with normal mononuclear haematopoietic cells ( P < 0·0001). Furthermore, high CXCR4-expression correlated with an unfavourable outcome in BCP- ALL (5-year cumulative incidence of relapse ± standard error: 38·4% ± 6·9% in CXCR4-high versus 12% ± 4·6% in CXCR4-low expressing cases, P < 0·0001). Interestingly, BM levels of the CXCR4-ligand ( CXCL12) were 2·7-fold lower ( P = 0·005) in diagnostic BCP- ALL samples compared with non-leukaemic controls. Induction chemotherapy restored CXCL12 levels to normal. Blocking the CXCR4-receptor with Plerixafor showed that the lower CXCL12 serum levels at diagnosis could not be explained by consumption by the leukaemic cells, nor did we observe an altered CXCL12-production capacity of BM-mesenchymal stromal cells ( BM- MSC) at this time-point. We rather observed that a very high density of leukaemic cells negatively affected CXCL12-production by the BM- MSC while stimulating the secretion levels of granulocyte colony-stimulating factor (G- CSF). These results suggest that highly proliferative leukaemic cells are able to down-regulate secretion of cytokines involved in homing ( CXCL12), while simultaneously up-regulating those involved in haematopoietic mobilization (G- CSF). Therefore, interference with the CXCR4/ CXCL12 axis may be an effective way to mobilize BCP- ALL cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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