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| Item Type: | Article |
|---|---|
| Title: | Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling |
| Creators Name: | Ihlow, J., Penter, L., Vuong, L.G., Bischoff, P., Obermayer, B., Trinks, A., Blau, O., Behnke, A., Conrad, T., Morkel, M., Wu, C.J., Westermann, J., Bullinger, L., von Brünneck, A.C., Blüthgen, N., Horst, D. and Praktiknjo, S.D. |
| Abstract: | BACKGROUND: Distinguishing donor- vs. recipient-derived myelodysplastic neoplasm (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is challenging and has direct therapeutical implications. METHODS: Here, we took a translational approach that we used in addition to conventional diagnostic techniques to resolve the origin of MDS in a 38-year-old patient with acquired aplastic anemia and evolving MDS after first allo-HSCT. Specifically, we used single-cell transcriptional profiling to differentiate between donor- and recipient-derived bone marrow cells and established a strategy that additionally allows identification of cells carrying the MDS-associated U2AF1(S34Y) variant. RESULTS: The patient exhibited mixed donor chimerism combined with severely reduced erythropoiesis and dysplastic morphology within the granulocytic and megakaryocytic lineage along with the MDS-associated U2AF1(S34Y) mutation in the bone marrow. Single-cell transcriptional profiling together with targeted enrichment of the U2AF1(S34Y)-specific locus further revealed that, while the immune compartment was mainly populated by donor-derived cells, myelopoiesis was predominantly driven by the recipient. Additionally, concordant with recipient-derived MDS, we found that U2AF1(S34Y)-mutated cells were exclusively recipient derived with X but not Y chromosome-specific gene expression. CONCLUSION: Our study highlights the clinical potential of integrating high-resolution single-cell techniques to resolve complex cases for personalized treatment decisions. |
| Keywords: | MDS, Allo-HSCT, Mixed Chimerism, Aplastic Anemia, Precision Diagnostics, Single-Cell, Targeted Sequencing, Mutational Profiling, U2AF1S34Y, Personalized Medicine |
| Source: | Med |
| ISSN: | 2666-6340 |
| Publisher: | Cell Press |
| Date: | 6 December 2024 |
| Official Publication: | https://doi.org/10.1016/j.medj.2024.11.001 |
| PubMed: | View item in PubMed |
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