Bogunia-Kubik K, Gieryng A, Dlubek D, Lange A
L Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Bone Marrow Transplant. 2009 Sep;44(5):273-8. doi: 10.1038/bmt.2009.30. Epub 2009 Mar 2.
The interaction between CXCL12 and its receptor CXCR4 plays a crucial role in the homing and mobilization of haematopoietic progenitors. We investigated the putative association between a CXCL12 gene polymorphism, the G --> A transition at position 801 in the 3'-untranslated region (3'UTR), and the yield of CD34(+) progenitors in 65 healthy allogeneic transplant donors who received G-CSF. Importantly, in this setting, the analysis was not biased by background disease or chemotherapy. The 3'UTR CXCL12 G801A polymorphism was detected using a PCR-RFLP technique with the MspI restriction enzyme and the frequency of CD34(+) progenitors was assessed by flow cytometry. The frequency as well as the number of CD34(+) progenitor cells in the first leukapheresis product was significantly higher from donors with the CXCL12-3'A allele compared to GG homozygotes (P<0.05 in both cases), especially for subjects with the CXCL12-3'AA homozygous genotype (P<0.01 in both cases). Moreover, more leukaphereses were needed to obtain the required number of CD34(+) progenitors for transplantation from CXCL12-3'GG homozygous donors compared to the CXCL12-3'A carriers (P=0.003). In conclusion, the CXCL12-3'A allele was associated with a higher yield of CD34(+) cells from healthy donors of PBPC for allogeneic haematopoietic SCT.
CXCL12与其受体CXCR4之间的相互作用在造血祖细胞的归巢和动员中起着关键作用。我们调查了CXCL12基因多态性(3'-非翻译区[3'UTR]第801位的G→A转换)与65名接受G-CSF的健康异基因移植供者中CD34(+)祖细胞产量之间的假定关联。重要的是,在这种情况下,分析不受背景疾病或化疗的影响。使用MspI限制性内切酶的PCR-RFLP技术检测3'UTR CXCL12 G801A多态性,并通过流式细胞术评估CD34(+)祖细胞的频率。与GG纯合子相比,携带CXCL12-3'A等位基因的供者首次白细胞分离产物中CD34(+)祖细胞的频率和数量显著更高(两种情况均P<0.05),尤其是CXCL12-3'AA纯合基因型的受试者(两种情况均P<0.01)。此外,与CXCL12-3'A携带者相比,从CXCL12-3'GG纯合供者获取移植所需数量的CD34(+)祖细胞需要更多次白细胞分离(P=0.003)。总之,CXCL12-3'A等位基因与异基因造血干细胞移植的外周血造血干细胞健康供者中CD34(+)细胞的更高产量相关。