Diagnostic and Prognostic Value of Mitochondrial DNA Minisatellites after Stem Cell Transplantation

Abstract

Mitochondrial DNA has been used to investigate phylogenetic relationships and pathophysiologic roles in aging, degenerative diseases, and cancer. We investigated the prognostic usefulness of mitochondrial DNA minisatellite (mtMS) markers compared with nuclear short tandem repeat markers by evaluating the laboratory performance and clinical value of these markers in a large sample of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with various simulated conditions in vitro and in serial follow-up samples. We examined the value of mtMS markers as a prognostic indicator in 100 patients with various hematologic disorders undergoing allo-HSCT, including 35 patients with longitudinal follow-up for 55 months. The mtMS markers showed high sensitivity and accuracy for the quantitative detection of chimerism compared with nuclear short tandem repeat markers, particularly in unrelated transplantation and under inappropriate sampling conditions. Longitudinal follow-up after allo-HSCT disclosed that chimerism precisely reflected the status of engraftment or relapse during the clinicopathological course. Moreover, changes in mtMS markers in recipients before allo-HSCT were associated with clinical outcomes. Our data indicate that mtMS markers have multiple functions in monitoring mixed chimerism and predicting prognosis after allo-HSCT.

Detection of Low Level Mixed Chimerism Using High Throughput SNP Genotyping

“…This is attributed to the hematopoiesis of the recipient's native CD34+ derived cells despite the cytoreductive treatment prior to the allograft transplant. Several studies have shown strong positive correlation between the extent of mixed chimerism and the likelihood of patient hematologic relapse [4,[6][7][8][9]. The magnitude of mixed chimerism is frequently measured using PCR-based methods [10,11] as a ratio of the recipient genotype signal to that of the donor.…”