Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling

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.; Praktiknjo, S.D.

Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling

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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
Volume:	6
Number:	4
Page Range:	100548
Date:	11 April 2024
Official Publication:	https://doi.org/10.1016/j.medj.2024.11.001
PubMed:	View item in PubMed

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