Hematology Unit, Galilee Medical Center, Nahariya & Bar-Ilan University Faculty of Medicine Safed, Israel.
Department of Hematology, Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Exp Hematol. 2018 Jul;63:17-21.e1. doi: 10.1016/j.exphem.2018.04.005. Epub 2018 Apr 26.
Increased chemokine C-X-C receptor 4 (CXCR4) expression is related to unfavorable outcome in chronic lymphocytic leukemia (CLL). Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that has been shown previously to interact with CXCR4 in neuronal cells. Here, we studied the in vitro effect of BDNF on CXCR4 expression and chemotaxis toward stromal derived factor-1 (SDF-1) in freshly isolated CLL cells. We also explored the correlations between serum BDNF levels in CLL patients and disease characteristics and clinical course. Incubation of CLL cells with recombinant BDNF (50 ng/mL) resulted in a downregulation of CXCR4 surface expression and atenuated chemotaxis toward SDF-1. Higher serum BDNF levels were associated with a mutated immunoglobulin heavy chain variable (IGHV) gene, an early clinical stage, and a stable clinical course. Our findings suggest that increased circulating blood BDNF may be associated with a favorable effect in CLL. However, the exact mechanism of this favorable effect should be investigated further.
趋化因子 C-X-C 受体 4（CXCR4）表达增加与慢性淋巴细胞白血病（CLL）的不良预后相关。脑源性神经营养因子（BDNF）是一种神经元生长因子，先前已证明其在神经元细胞中与 CXCR4 相互作用。在这里，我们研究了 BDNF 在体外对新鲜分离的 CLL 细胞中 CXCR4 表达和对基质衍生因子-1（SDF-1）趋化性的影响。我们还探讨了 CLL 患者血清 BDNF 水平与疾病特征和临床病程之间的相关性。用重组 BDNF（50ng/ml）孵育 CLL 细胞可导致 CXCR4 表面表达下调，并减弱对 SDF-1 的趋化性。较高的血清 BDNF 水平与突变的免疫球蛋白重链可变（IGHV）基因、早期临床阶段和稳定的临床病程相关。我们的研究结果表明，循环血液中 BDNF 的增加可能与 CLL 的有利影响相关。然而，这种有利影响的确切机制仍需进一步研究。
