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. PURPOSE: 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. CONCLUSION: Our findings suggest that CXCL12 may have a role in leukaemic cell proliferation and survival during childhood ALL.