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Bone marrow mesenchymal stromal cells remain of recipient origin after allogeneic SCT and do not harbor the JAK2V617F mutation in patients with myelofibrosis

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Abstract

The close association of the myeloproliferative neoplasms with the activating non-receptor tyrosine kinase JAK2V617F mutation is well established. To further clarify the pathomechanisms of this mutation in patients with myelofibrosis, we performed screening with quantitative real-time PCR for the respective mutation in in vitro expanded bone marrow (BM) mesenchymal stromal cells (MSCs) and compared the results with BM/peripheral blood (PB). Eight patients with primary/secondary myelofibrosis were investigated before (n = 4) or after allogeneic stem cell transplantation (n = 4). All patients had systemic evidence of the JAK2V617F mutation in BM/PB (mutation ratios 0.2–23.5) at the time of investigation in contrast to negative results in the MSCs (n = 7) or a very low (0.004) mutation ratio (n = 1) which was probably due to hematopoietic contamination. The four patients post-transplant had systemic donor chimerism between 96.5 and 100% in BM/PB, while MSCs showed no evidence of donor-specific alleles. In conclusion, in myelofibrosis, the JAK2V617F mutation is restricted to hematopoietic cells, and cannot explain the stromal alterations being observed in this disorder. Further, the MSCs remain of recipient origin after allogeneic SCT, which might contribute to the increased risk of graft dysfunction or failure in myelofibrosis patients after allogeneic transplantation.

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Acknowledgments

The authors would like to thank Silke Zeschke, Ulrike Larsen, and Sandra Hannemann from the department’s laboratory for excellent technical assistance. Haefaa Alchalby is supported by an EBMT-AMGEN fellowship.

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Authors and Affiliations

  1. Interdisciplinary Clinic for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), Martinistr. 52, 20246, Hamburg, Germany

    Ulrike Bacher, Svetlana Asenova, Anita Badbaran, Axel Rolf Zander, Haefaa Alchalby, Boris Fehse, Nicolaus Kröger, Claudia Lange & Francis Ayuk

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  1. Ulrike Bacher
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  2. Svetlana Asenova
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  3. Anita Badbaran
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  4. Axel Rolf Zander
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  5. Haefaa Alchalby
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  6. Boris Fehse
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  7. Nicolaus Kröger
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  8. Claudia Lange
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  9. Francis Ayuk
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Correspondence to Ulrike Bacher.

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Bacher, U., Asenova, S., Badbaran, A. et al. Bone marrow mesenchymal stromal cells remain of recipient origin after allogeneic SCT and do not harbor the JAK2V617F mutation in patients with myelofibrosis. Clin Exp Med 10, 205–208 (2010). https://doi.org/10.1007/s10238-009-0058-9

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  • DOI: https://doi.org/10.1007/s10238-009-0058-9

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