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Donor CSF3R with the rs3917980A/G or G/G genotype is correlated with better leukemia-free survival after allogenic hematopoietic stem cell transplantation

Genes & Immunity volume 23, pages 166–174 (2022)Cite this article

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Abstract

Polymorphisms in the granulocyte colony-stimulating factor receptor gene (GCSFR, CSF3R) have been reported to be associated with peripheral blood stem cell enrichment and hematological diseases. The aim of our study was to investigate the effects of donor CSF3R allelic polymorphisms on the outcomes of allogeneic stem cell transplantation. A total of 273 patients who were diagnosed with hematological diseases and treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT) were enrolled in this study. Single-nucleotide polymorphisms in CSF3R were genotyped by targeted next-generation sequencing. There were six types of CSF3R genotypes with percentages over 1%. LFS and OS analyses showed that recipients receiving grafts from healthy donors with a rs3917980 G/G or A/G genotype had higher LFS rates than those receiving grafts from donors carrying a rs22754272 T/C genotype and the double-negative group (p = 0.036). Univariate cox analysis showed that donor CSF3R with the rs2275472 T/C genotype was associated with higher transplantation-related mortality (TRM) rates (HR = 2.853, 95% CI: 1.405–5.792, p = 0.00371) and lower rates of leukemia-free survival (LFS) (HR = 1.846; 95% CI: 1.018–3.347, p = 0.0435). In addition, donor CSF3R with the rs3917980G/G or A/G genotype was associated with better overall survival (OS) rates (HR = 0.560, 95% CI: 0.3162–0.9916, p = 0.047) and lower TRM rates (HR = 0.497, 95% CI: 0.2628–0.9397, p = 0.0315). Furthermore, multivariate cox analysis found that rs2275472 T/C genotype was an independent risk factors for TRM rates (HR = 3.210, 95% CI: 1.573–6.55, p = 0.001), while no statistical difference was found between rs3917980G/G or A/G genotype and clinical outcomes. Our findings demonstrate the important prognostic value of genetic variations in donor CSF3R to predict clinical outcomes in patients undergoing allo-HSCT.

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Fig. 1: The frequency of healthy donors’CSF3R SNPs distributed among the recipients with different diagnoses (n = 273).
Fig. 2: The associations of CSF3R SNPs with TRM and relapse.
Fig. 3: The association between overall survival and LFS probabilities and rs3917980 and rs2275472 polymorphisms.
Fig. 4: Multifactor Cox regression of different clinical outcomes.
Fig. 5: Analysis of LFS and OS among CSF3R SNPs.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 82070184, 81870140, 81870137), the National Key Research and Development Program of China (Nos. 2017YFA0104500, 2021YFC2500300); Scientific Research Foundation for Capital Medicine Development (No. 2018-2-4084) Beijing Municipal Science & Technology Commission (No. Z171100001017098). The authors thank the members of the core facilities at the Peking University Institute of Hematology for the sample collection.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China

    Xun-Hong Cao, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Kai-Yan Liu, Xiao-Jun Huang, Ying-Jun Chang, Xiang-Yu Zhao & Xiao-Su Zhao

  2. Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China

    Yan Hong & Xingxing Yu

  3. Collaborative Innovation Center of Hematology, Peking University, Beijing, China

    Xiao-Su Zhao

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  1. Xun-Hong Cao
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Contributions

XZ and X-SZ designed the study; XC performed data analysis; XC, YH, XY, LX, XZ, YW, KL, XH, and YC participated in the information collection of donors and patients. XC drafted the manuscript. All authors read and approved the final version.

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Correspondence to Xiang-Yu Zhao or Xiao-Su Zhao.

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Cao, XH., Hong, Y., Yu, X. et al. Donor CSF3R with the rs3917980A/G or G/G genotype is correlated with better leukemia-free survival after allogenic hematopoietic stem cell transplantation. Genes Immun 23, 166–174 (2022). https://doi.org/10.1038/s41435-022-00177-5

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