A single-cell solution to a transplant mystery

Area of Science:

• Hematology
• Genomics
• Transplantation immunology

Background:

• Myelodysplastic neoplasms (MDS) can arise after allogeneic hematopoietic stem cell transplantation (HSCT).
• Distinguishing donor- versus recipient-derived clones is crucial for guiding treatment but can be challenging with conventional methods.

Purpose of the Study:

• To investigate the origin of a post-transplant myelodysplastic neoplasm clone.
• To demonstrate the utility of tailored single-cell sequencing in resolving complex diagnostic dilemmas in HSCT recipients.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) for transcriptome profiling.
• Targeted sequencing enrichment for the U2AF1 gene mutation.
• Integration of genomic and transcriptomic data to determine clone origin.

Main Results:

• Conventional diagnostics were insufficient to determine the clonal origin.
• scRNA-seq combined with U2AF1 enrichment successfully identified the mutant clone as recipient-derived.
• Accurate diagnosis facilitated appropriate therapeutic decisions.

Conclusions:

• Tailored single-cell sequencing is a powerful tool for diagnosing challenging cases of post-transplant malignancy.
• Identifying the clonal origin is critical for effective management of HSCT complications.
• This approach guided a successful second transplant, resulting in remission.