study of chemokine receptor "CCXCR4" expression as an indicator for significant extramedullary organ infiltration in childhood acute lymphoblastic leukemia

ABSTRACT

CXCR4 is a G-protein linked seven transmembrane spanning chemokine receptor that binds stromal cell-derived factor-1 [SDF-1]. CXCR4 plays a crucial role in the survival and trafficking of leukemia cells. Childhood acute lymphoblastic leukemia [ALL] is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potent mechanism in the trafficking of leukemia cells is in the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells and its ligand stromal cell-derived factor-1 [SDF-1], produced by stromal cells in bone marrow and extramedullary organs. To evaluate the predictive value of high expression of CXCR4 receptor for extramedullary organ infiltration in childhood ALL. The study was conducted on 32 patients with newly diagnosed ALL and 15 healthy children as a control. The 32 studied patients were 18 males [56.3%] and 14 females [43.8%], age ranged from 1.7 years to 17 years, with a mean value of 6.18 +/- 4.38 years. Significant extramedullary organ infiltration was found in 8 patients [25%]. Flowcytometric analysis was used to measure CXCR4 expression on bone marrow lymphoblasts in ALL patients, and on normal peripheral blood lymphocytes in control subjects. CXCR4 expression was statistically significantly higher [p<0.001] in patients compared with control group CXCR4 expression with extramedullary organ infiltration [mean 56.47 +/- 20.54], when compared with patients without significant extramedullary organ infiltration [mean 20.58 +/- 7.42]. High expression of CXCR4 receptor has a predictive value for extramedullary organ infiltration in childhood ALL. Pharmacological agents affecting CXCR4 may have a potential therapeutic effect in the management and outcome of the disease