Mitochondrial DNA spectra of single human CD34+ cells, T cells, B cells, and granulocytes

Mitochondria in hematopoiesis and hematological diseases

“…Single mutant mtDNA molecules have long been assumed to be lost by dilution in rapidly dividing tissues such as bone marrow. Actually, agedependent accumulation of mtDNA mutations, and expansion of mutated mtDNA molecules from heteroplasmy to homoplasmy (Chinnery et al, 2002), appear to be relatively common in adult CD34 þ marrow progenitors and presumably stem cells (Ogasawara et al, 2005). Thus, age-associated mtDNA mutations lead to marked heterogeneity among adult bone marrow and peripheral blood CD34 þ cells, not present in umbilical cord blood.…”

Mitochondrial DNA sequence variation in single cells from leukemia patients

“…We have recently described age-dependent accumulation of mtDNA mutations in single hematopoietic cells from the bone marrow and peripheral blood (PB) of healthy donors [19][20][21] and compared the mutation spectra of differentiated blood cells from the same donors by using an optimized method for analyzing mtDNA variation in single flow cytometry-sorted cells. 21 In the present study, we used single-cell analysis to detect lowfrequency individual somatic mutations that are not well represented in bulk tissue to quantify a somatic mutation process in leukemia, as well as to determine whether mtDNA could be used as a marker for monitoring disease progression.…”

Mitochondrial DNA minisatellites as new markers for the quantitative determination of hematopoietic chimerism after allogeneic stem cell transplantation

“…2 To overcome these barriers, pegylated forms of rIFN-a (Peg-rIFN-a) have recently been explored as treatment options for patients with PV. 5,6 Peg-rIFN-a appears to be safe, non-leukemogenic and well tolerated, although adverse events including fever, thrombocytopenia and headache are not infrequent.…”

“…Fifty-five to 60% of genetic alterations in CD34 þ cells, T cells and B cells were length changes in the homopolymeric C tract at np 303-315 in HV2. 6 Therefore, heterogeneity of the mtDNA sequence in normal adult CD34 þ cells might have implications such as, a natural genetic 'marker' of hematopoietic progenitors and stem cells to estimate the number of active stem cells in the steady state. 7 The patterns of mutations that have accumulated over time along the transmission of the mtDNA lineage give rise to differences between individuals, and have become the basis for forensic discrimination.…”

“…6,7 In a phase 2 trial of Peg-rIFN-a 2a in PV, Kiladjian et al 5 performed a prospective sequential quantitative evaluation of the percentage of mutated JAK2 allele (%JAK2V617F) using real-time polymerase chain reaction (PCR). The %JAK2V617F was observed to be decreased in 24 of 27 treated patients.…”