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对大型单中心相关供者队列的分析未能发现 SDF1/CXCR4 或 VCAM/VLA4 基因多态性与 G-CSF 反应后造血祖细胞动员水平之间的关系。

Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF.

机构信息

Institut Paoli-Calmettes, Comprehensive Cancer Center, Marseille, France.

Aix-Marseille Univ, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.

出版信息

PLoS One. 2020 Mar 5;15(3):e0228878. doi: 10.1371/journal.pone.0228878. eCollection 2020.

Abstract

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.

摘要

我们研究了一组 367 名健康相关的供体,他们自愿捐献造血干细胞进行异基因移植。所有供体均在单一机构接受同质护理,并在接受单采术前行 rhG-CSF 动员治疗。外周血 CD34+ 细胞计数被用作 rhG-CSF 诱导动员的主要替代标志物。我们研究了位于对动员功能重要的产物基因中的已知遗传多态性个体间变异是否会影响 CD34+动员的程度,无论是单独还是组合。我们发现 SDF1、CXCR4、VCAM 和 VLA4 基因的单个 SNP 或单倍型对 CD34+细胞计数的影响很小或没有影响,无论是将 CD34+细胞计数作为连续变量还是分类变量。简单描述供体的临床特征,如体重指数、年龄和性别等,是干细胞动员的更有力预测因子。我们的队列在遗传分析方面仍然相对较小,但与之前发表的报告中分析的队列相比具有优势,这些报告表明遗传特征与 rhG-CSF 反应之间存在关联;尽管存在这一限制,但在存在多个潜在供体供一个给定患者选择时,我们的数据不支持使用遗传分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9b2/7058310/3dd76d7630b7/pone.0228878.g002.jpg

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