Abstract 464: CXCR7 protein is strongly expressed in B-acute lymphoblastic leukemia (ALL) but not in T-ALL or acute myelogenous leukemia

The identification of CXCR7 in addition to CXCR4 as a receptor for the chemokine CXCL12/SDF-1 and recent reports that CXCR7 is expressed in many cancers including breast, lung and prostate prompted us to evaluate the role of CXCR7 in hematological malignancies. While CXCR4 is known to be involved in the progression of acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML), the role of CXCR7 in leukemic dissemination remains unknown. Using immunohistochemistry, we evaluated the expression patterns of CXCR7 and CXCR4 in tissue microarrays (TMAs) constructed from bone marrow biopsies obtained from patients diagnosed with pre B- and B-ALL (n=75; median age 5 yrs, range 6 mo-72 yrs), T-ALL (n=11; median age 12 yrs, range 4-29 yrs) and AML (n=140; median age 62 yrs, range 1-83 yrs). CXCR7 expression was also evaluated at the gene and protein levels in peripheral blood mononuclear cells from ALL and AML patients and in B-cell lines (Raji, NC-37, Ramos, Nalm-6, Reh), T-cell lines (Jurkat, Hut-102B, Sez-4, CEM), and myeloid cell lines (KG-1, HL-60, THP-1, U-937, K562, HEL) using RT-PCR and flow cytometry. We found that in B-and preB-ALL TMAs, CXCR7 was immunopositive in 79% of the patients, in contrast to negative immunostaining in 100% of T-ALL and AML samples. Consistently, flow cytometry showed that CXCR7 protein is expressed on the surface of preB-ALL cells, but not on T-ALL, AML or normal controls. CXCR7 surface expression in the cell lines studied showed that three (NC-37, Raji, Reh) out of five B-cell lines expressed CXCR7, but not in any of the T-cell lines, and only weakly in one (KG-1) of six myeloid cell lines studied. Analysis of the functional role of CXCR7 in leukemia revealed that CXCR7 did not mediate chemotaxis of CXCR7-positive NC-37 B-cell line and CXCR7-negative HL-60 myeloid cell line towards an SDF-1 gradient. However, CXCR7 was found to mediate the trans-endothelial migration, adhesion to HUVEC and survival of NC-37 cells, but not the adhesion to HUVEC or survival of HL-60 cells. In conclusion, the selective strong expression of CXCR7 in B-ALL but not in T-ALL or AML suggests a differential role this protein may play in various types of leukemia. As CXCR7 mediates trans-endothelial migration, adhesion and survival of B-cell line, further investigations into the functional role of CXCR7 in primary B-ALL are warranted with the aim of identifying new therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. I