[Significance of CXCL12/CXCR4 expression in T-lymphoblastic lymphoma/leukemia]

Objective: To investigate the significance of CXCL12/CXCR4 expression in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its prognostic significance. Methods: Using immunohistochemical EnVision method, CXCL12, CXCR4 and Ki-67 expression were evaluated in 72 cases of T-LBL/ALL and 30 selected cases of lymph node reactive hyperplasia (LH) as control. In addition, CXCL12 and CXCR4 mRNA expression levels were examined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. Results: Immunohistochemical results showed that the expression rates of CXCL12 and CXCR4 in T-LBL/ALL were 84.7%(61/72) and 91.6%(66/72), respectively, and these were not different from the expression in the LH control group. The expression indexes of Ki-67 <80% and ≥80% were 25 cases (34.7%, 25/72) and 47 cases (65.3%, 47/72), respectively. Real-time quantitative PCR demonstrated that CXCL12 and CXCR4 mRNA expression in T-LBL/ALL was 62.4% and 71.5%, respectively, and was statistically different (P<0.05) from that of the control group. Single factor analysis found that CXCL12 mRNA expression in T-LBL/ALL was positively correlated with Ann Arbor staging and KPS score (P<0.05); CXCL12 protein expression was positively correlated with splenomegaly (P<0.05); CXCR4 mRNA expression was positively correlated with the IPI score, clinical symptoms, mediastinal widening and bone marrow involvement (P<0.05); CXCR4 protein expression was positively correlated with mediastinal widening (P<0.05); CXCL12 mRNA expression was positively correlated with CXCL12 protein and CXCR4 protein expression (P<0.05), but not the CXCR4 mRNA and protein levels. There was no correlation between CXCL12 and CXCR4 protein expression and CXCR4 mRNA expression. Multivariate COX regression analysis showed that high expression of CXCR4 protein, hepatosplenomegaly and bone marrow involvement were risk factors for T-LBL/ALL outcome. Conclusions: CXCL12/CXCR4 expression is associated with disease progress, mediastinal widening, bone marrow involvement and adverse outcome in T-LBL/ALL. CXCL12/CXCR4 axis plays an essential role in the occurrence and development of T-LBL/ALL. However, CXCL12 and CXCR4 protein expression are not entirely reflected by mRNA transcription levels, and there may be other molecules involved in CXCL12/CXCR4 expression and regulation. With CXCR4 antagonists undergoing clinical trials, targeting the CXCL12/CXCR4 axis may be a promising treatment strategy for T-LBL/ALL.