Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor
Hematopoietic stem and progenitor cells (HSPC) from mobilized blood are the preferred graft source for allogeneic and autologous stem cell transplantation. The efficiency of CD34+ cell mobilization with granulocyte colony-stimulating factor (G-CSF) varies significantly between individuals, but is r...
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| Format: | Article |
| Language: | English |
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Ferrata Storti Foundation
2025-06-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/12096 |
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| author | Miriam Stenzinger Susanne Beck Iordanis Ourailidis Anna-Lena Volckmar Nagarajan Paramasivam Aysel Ahadova Aitzkoa Lopez de Lapuente Portilla Phuong La Yen Bjorn Nilsson Justo Lorenzo Bermejo Halvard Bonig Jan Budczies |
| author_facet | Miriam Stenzinger Susanne Beck Iordanis Ourailidis Anna-Lena Volckmar Nagarajan Paramasivam Aysel Ahadova Aitzkoa Lopez de Lapuente Portilla Phuong La Yen Bjorn Nilsson Justo Lorenzo Bermejo Halvard Bonig Jan Budczies |
| author_sort | Miriam Stenzinger |
| collection | DOAJ |
| description |
Hematopoietic stem and progenitor cells (HSPC) from mobilized blood are the preferred graft source for allogeneic and autologous stem cell transplantation. The efficiency of CD34+ cell mobilization with granulocyte colony-stimulating factor (G-CSF) varies significantly between individuals, but is reproducible across mobilization cycles within an individual, suggesting a genetic component, a hypothesis that has been previously investigated by testing for candidate single-nucleotide polymorphisms (SNP) associations. As the genetic determinants of HSPC mobilization have not been analyzed on the genomic scale so far, we performed a genome-wide association study (GWAS) in a German population of 564 healthy G-CSF mobilized allogeneic stem cell donors.
None of the association between about 5 million variants and the primary outcome investigated (CD34+ cell frequency in peripheral blood) reached genome-wide significance. Focused analysis of 11 variants previously shown to be associated with basal CD34+ cell levels confirmed an association of CXCR4-rs11688530 (A>G) and ARHGAP45-rs36084354 (A>G) with higher CD34+ frequency in G-CSF mobilized healthy donors showing an explained variance of 1.07% (p=0.004) and 0.86% (p=0.01), respectively. Demographic analysis revealed an association of peripheral blood CD34+ cell frequency with sex (Varex = 8.1%) and BMI (Varex = 7.2%) that exceeded the contribution of single variants.
The current study is the first GWAS in mobilized stem cell donors and had a statistical power of 80% to detect SNPs with explained variance of ≥6.7% at genome-wide significance. The study results exclude a monogenetic cause of population G-CSF responsiveness and support the view that polygenetic risk scores are required as predictors.
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| format | Article |
| id | doaj-art-d95f0b2611e645d2bea66b1f5fec7edd |
| institution | OA Journals |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-d95f0b2611e645d2bea66b1f5fec7edd2025-08-20T02:32:26ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-06-01999110.3324/haematol.2025.287637Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factorMiriam Stenzinger0Susanne Beck1Iordanis Ourailidis2Anna-Lena Volckmar3Nagarajan Paramasivam4Aysel Ahadova5Aitzkoa Lopez de Lapuente Portilla6Phuong La Yen7Bjorn Nilsson8Justo Lorenzo Bermejo9Halvard Bonig10Jan Budczies11Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany; Institute for Clinical Transfusion Medicine and Cell Therapy, HeidelbergInstitute of Pathology, University Hospital Heidelberg, HeidelbergInstitute of Pathology, University Hospital Heidelberg, HeidelbergInstitute of Pathology, University Hospital Heidelberg, HeidelbergComputational Oncology Group, Molecular Precision Oncology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT) Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, HeidelbergDepartment of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, HeidelbergDepartment of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, LundDepartment of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, LundDepartment of Laboratory Medicine, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Broad Institute, Cambridge, MAStatistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany; Laboratory of Biostatistics for Precision Oncology, Institut de cancerologie Strasbourg Europe, StrasbourgInstitute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt a. M., Germany; German Red Cross Blood Service Baden-Wurttemberg-Hessen, Institute Frankfurt, Frankfurt a. M.Institute of Pathology, University Hospital Heidelberg, Heidelberg Hematopoietic stem and progenitor cells (HSPC) from mobilized blood are the preferred graft source for allogeneic and autologous stem cell transplantation. The efficiency of CD34+ cell mobilization with granulocyte colony-stimulating factor (G-CSF) varies significantly between individuals, but is reproducible across mobilization cycles within an individual, suggesting a genetic component, a hypothesis that has been previously investigated by testing for candidate single-nucleotide polymorphisms (SNP) associations. As the genetic determinants of HSPC mobilization have not been analyzed on the genomic scale so far, we performed a genome-wide association study (GWAS) in a German population of 564 healthy G-CSF mobilized allogeneic stem cell donors. None of the association between about 5 million variants and the primary outcome investigated (CD34+ cell frequency in peripheral blood) reached genome-wide significance. Focused analysis of 11 variants previously shown to be associated with basal CD34+ cell levels confirmed an association of CXCR4-rs11688530 (A>G) and ARHGAP45-rs36084354 (A>G) with higher CD34+ frequency in G-CSF mobilized healthy donors showing an explained variance of 1.07% (p=0.004) and 0.86% (p=0.01), respectively. Demographic analysis revealed an association of peripheral blood CD34+ cell frequency with sex (Varex = 8.1%) and BMI (Varex = 7.2%) that exceeded the contribution of single variants. The current study is the first GWAS in mobilized stem cell donors and had a statistical power of 80% to detect SNPs with explained variance of ≥6.7% at genome-wide significance. The study results exclude a monogenetic cause of population G-CSF responsiveness and support the view that polygenetic risk scores are required as predictors. https://haematologica.org/article/view/12096 |
| spellingShingle | Miriam Stenzinger Susanne Beck Iordanis Ourailidis Anna-Lena Volckmar Nagarajan Paramasivam Aysel Ahadova Aitzkoa Lopez de Lapuente Portilla Phuong La Yen Bjorn Nilsson Justo Lorenzo Bermejo Halvard Bonig Jan Budczies Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor Haematologica |
| title | Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor |
| title_full | Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor |
| title_fullStr | Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor |
| title_full_unstemmed | Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor |
| title_short | Contribution of genetics to hematopoietic stem cell mobilization: a genome-wide association study of 564 healthy donors mobilized with granulocyte colony-stimulating factor |
| title_sort | contribution of genetics to hematopoietic stem cell mobilization a genome wide association study of 564 healthy donors mobilized with granulocyte colony stimulating factor |
| url | https://haematologica.org/article/view/12096 |
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