CXCR3型
趋化因子
癌症研究
趋化因子受体
免疫学
CXCL10型
趋化性
白血病
医学
生物
受体
内科学
炎症
作者
Ana M. Gómez,Carolina Martínez,Miguel González,Alfonso Luque,Gustavo J. Melen,J. Larrauri Martínez,Sonsoles Hortelano,Álvaro Lassaletta,Lucas Moreno,Manuel Ramı́rez
标识
DOI:10.1016/j.bcmd.2015.07.001
摘要
We studied whether chemokines may have a role in relapses in childhood acute lymphoblastic leukemia (ALL). We compared the levels of chemokine receptors in marrow samples from 82 children with ALL at diagnosis versus 15 at relapses, and quantified the levels of chemokines in central system fluid (CSF) samples. The functional role of specific chemokines was studied in vitro and in vivo. The expression of some chemokine receptors was upregulated upon leukemic relapse, both in B- and in T-ALL, and in cases of medullary and extramedullary involvement. CXCL10 induced chemotaxis in leukemic cell lines and in primary leukemic cells, depending upon the levels of CXCR3 expression. CXCL10 specifically diminished chemotherapy-induced apoptosis on ALL cells expressing CXCR3, partially inhibiting caspase activation and maintaining the levels of the antiapoptotic protein Bcl-2. Finally, immunodeficient mice engrafted with CXCR3-expressing human leukemic cells showed decreased infiltration of marrow, spleen, and CNS after receiving a CXCR3-antagonist molecule. CXCR3 signaling in ALL may have a dual function: chemotactic for the localisation of leukemic blasts in specific niches, and it may also confer resistance to chemotherapy, enhancing the chances for relapses.
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