Quantifying HLA transcripts by genotype in chimeric mixtures at single-cell resolution.

Area of Science:

• Immunogenetics
• Molecular Biology
• Oncology

Background:

• Major histocompatibility locus (HLA) genes are crucial for immune surveillance and self-recognition.
• Alterations in HLA post-allogeneic hematopoietic cell transplantation (alloHCT) can lead to disease recurrence.
• Current HLA transcript quantification methods lack single-cell sensitivity, limiting clinical application.

Purpose of the Study:

• To introduce scrHLA-typing, a novel technique for precise single-cell HLA transcript identification and quantification.
• To assess the clinical utility of scrHLA-typing in patients experiencing post-transplant relapse.

Main Methods:

• Development of scrHLA-typing utilizing long-read sequencing technology.
• Application of scrHLA-typing to patient samples with post-transplant relapse.
• Analysis of HLA allele-specific expression in residual leukemia cells.

Main Results:

• scrHLA-typing accurately identified and quantified HLA transcripts at the single-cell level.
• The method detected HLA allele-specific expression across varying levels of donor-recipient chimerism.
• Distinct HLA expression patterns were identified in residual leukemia cells among different patients.

Conclusions:

• scrHLA-typing offers clinically actionable insights into HLA expression in single cells.
• This technique has the potential to improve risk stratification for patients undergoing alloHCT.
• scrHLA-typing can guide the selection of personalized salvage therapies to enhance treatment strategies after relapse.