Chemokine CXCL12 enhances proliferation in pre-B-ALL via STAT5 activation.
BACKGROUND
CXCL12 (SDF-1alpha) is a chemokine, which plays an important role in normal B-cell lymphopoesis, migration and homing to the bone marrow (BM) and previous studies have suggested a role for CXCL12 and its receptor CXCR4 in the pathogenesis of ALL.


OBJECTIVE
CXCL12 levels in serum were evaluated from ALL-children and controls. The biological effect of recombinant CXCL12 on primary leukaemic cells was investigated. Signalling via the CXCL12/CXCR4 axis was further characterized in an in vitro model using the pre-B leukaemic cell line Nalm-6.


RESULTS
The serum level of CXCL12 in children at diagnosis of pre-B-ALL is significantly higher than in healthy children (4.8 (0-32) ng/ml vs. 0 (0-3.2) ng/ml, P < 0.001). After completed chemotherapy, CXCL12 decreases to levels comparable to those found in the control group. In addition, we found that recombinant CXCL12 enhances pre-B leukaemic cell proliferation in vitro. The CXCL12/CXCR4 axis is able to initiate functional signalling and we show that STAT5 is activated in CD19+ leukaemic cells from BM of ALL patients and in the leukaemic cell line Nalm-6.


CONCLUSIONS
Our findings suggest that CXCL12 may have a role in leukaemic cell proliferation and survival during childhood ALL.
Mowafi
Frida
F
Microbiology Tumour Biology Center, Karolinska Institutet, Stockholm, Sweden.
Cagigi
Alberto
A
Matskova
Ludmila
L
Björk
Olle
O
Chiodi
Francesca
F
Nilsson
Anna
A
D000293:Adolescent; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000097:blood* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D054448:Precursor Cells, B-Lymphoid / Q000473:pathology; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor