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British journal of haematology, 2014-07, Vol.166 (2), p.240-249
Erscheinungsjahr
2014
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ)
Beschreibungen/Notizen
Summary
Malignant cells infiltrating the bone marrow (
BM
) interfere with normal cellular behaviour of supporting cells, thereby creating a malignant niche. We found that
CXCR
4‐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
CXCR
4‐expression correlated with an unfavourable outcome in
BCP
‐
ALL
(5‐year cumulative incidence of relapse ± standard error: 38·4% ± 6·9% in
CXCR
4‐high
versus
12% ± 4·6% in
CXCR
4‐low expressing cases,
P
<
0·0001). Interestingly,
BM
levels of the
CXCR
4‐ligand (
CXCL
12) were 2·7‐fold lower (
P
=
0·005) in diagnostic
BCP
‐
ALL
samples compared with non‐leukaemic controls. Induction chemotherapy restored
CXCL
12 levels to normal. Blocking the
CXCR
4‐receptor with Plerixafor showed that the lower
CXCL
12 serum levels at diagnosis could not be explained by consumption by the leukaemic cells, nor did we observe an altered
CXCL
12‐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
CXCL
12‐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 (
CXCL
12), while simultaneously up‐regulating those involved in haematopoietic mobilization (G‐
CSF
). Therefore, interference with the
CXCR
4/
CXCL
12 axis may be an effective way to mobilize
BCP
‐
ALL
cells.
Sprache
Englisch
Identifikatoren
ISSN: 0007-1048
eISSN: 1365-2141
DOI: 10.1111/bjh.12883
Titel-ID: cdi_crossref_primary_10_1111_bjh_12883
Format
–
Weiterführende Literatur
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