New precision diagnostic approach for myelodysplastic neoplasm

Porträt photo Samantha Praktiknjo — © privat

Researchers at the Berlin Institute of Health at Charité (BIH) and Charité - Universitätsmedizin Berlin have developed a customized single-cell approach that enables precision diagnostics in myelodysplastic neoplasia. In an interview, Dr. Samantha Praktiknjo, head of the study and last author of the publication, talks about her research results.

What question did you want to answer, what were you particularly interested in?

In a myelodysplastic neoplasm (MDS), genetic changes lead to impaired blood cell formation, which is associated with an increased risk of acute myeloid leukemia. MDS can also occur after allogeneic hematopoietic stem cell transplantation. In such cases, it is particularly important for further treatment to determine whether the MDS originates from recipient or donor cells. However, a major problem is that conventional diagnostics and standardized methods usually cannot answer this question adequately. This was illustrated by the case of a seriously ill young patient here at Charité who faced this clinical scenario. Despite exhausting all diagnostic possibilities, the origin of her MDS could not be determined. This prompted us to develop a methodological approach that would enable a clear diagnosis and differentiation between recipient- and donor-derived MDS.

Photo shows Dysplastic megakaryocytes in the bone marrow of the patient suffering from MDS — Dysplastic megakaryocytes in the bone marrow of the patient suffering from MDS© Jana Ihlow

What specific challenges did you face when developing your approach?

A significant limitation is that, although gene mutations can be identified using so-called bulk methods, these cannot be traced to individual cells. Standardized and commercial single-cell methods are typically designed to read only a short sequence region from one end of the mRNA. However, many mutations are located not only at the ends but also in the middle of a gene sequence, making them difficult or impossible to detect. This was also the case with our patient, in whom an MDS-associated U2AF1 mutation had already been identified. However, it was unclear whether the mutated cells originated from the recipient or the donor. To answer this question, we developed a single-cell strategy that specifically detects and enriches the relevant mutation. In addition to distinguishing between donor and recipient cells, our approach enables genotyping of each cell based on its mutational status. This allowed us to clearly demonstrate that the mutated cells originated from the patient.

What surprised you and why? What was new?

We were pleasantly surprised that we were able to provide precision diagnostics in a relatively short time, which in turn enabled targeted and personalized therapy.

What significance could this success have for future patients?

The approach we have established could be groundbreaking for helping similarly affected patients and, in principle, can also be adapted for high-resolution investigation of other disease-specific mutations.

Where do you see the translational bridge between research and application?

Making the latest molecular methods available for clinical use is both a challenge and an opportunity. This requires the development and implementation of tailored approaches to answer specific questions that cannot be addressed with existing diagnostics or standardized methods. Furthermore, our study highlights the importance of a 'bedside to bench to bedside' approach-both to identify translational research needs and to enable personalized medicine in the clinical setting.

Link to the publication

Ihlow et al. (2025). Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling.