Tracking of donor and recipient immune and leukemia phenotypes after allogeneic stem cell transplantation using mitochondrial DNA mutations. [ASAP-Seq 2]

Mitochondrial DNA mutations (mtDNA) enable deconvolution of donor- and recipient-derived single cell profiles. Here, we provide examples for sensitive donor-recipient deconvolution of peripheral blood and bone marrow ASAP-seq profiles in the context of incipient and overt AML relapse following allogeneic hematopoietic stem cell transplantation. Further, using single cell DNA sequencing (Tapestri), we demonstrate co-evolution of mtDNA and somatic nuclear DNA mutations in relapsed CLL post-HSCT. Staining of bone marrow or peripheral blood-derived single cells with oligotags for detection of surface marker expression using Total-seq A, B or D followed by single cell ATAC with select antigen profiling by sequencing (ASAP-seq) or single cell DNA sequencing using the Tapestri platform (Mission Bio).