AbstractBackgroundCXCL12 (SDF‐1α) 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.PurposeCXCL12 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.ResultsThe 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.ConclusionOur findings suggest that CXCL12 may have a role in leukaemic cell proliferation and survival during childhood ALL. Pediatr Blood Cancer 2008;50:812–817. © 2007 Wiley‐Liss, Inc.