Changes of telomere length in children after hematopoietic stem cell transplantation

Abstract

Summary:but can also suggest the replicative potential remaining in each cell.14 Recovery of the hematopoietic system after hematopoTelomeres are responsible for keeping the stability not only of chromosomes but also of genes. To investigate ietic stem cell transplantation (HSCT) requires numerous replication cycles by HSCs. Such successive division of the effect of hematopoietic stem cell transplantation (HSCT) on telomeres, we studied telomere length in the HSCs may affect the telomere length of their descendant cells. Since telomeres are important not only for the stabperipheral blood mononuclear cells of 31 children who received HSCT. In the auto-HSCT groups telomere ility of chromosomes and genes, but also for determining the fate of cells [15][16][17][18][19] we became interested in the effect of length ranged from 8.6 to 12.0 kb and in the allo-HSCT groups from 8.4 to 12.0 kb. Comparison of the telomere HSCT on telomere length. In this study, we assessed the effect of HSCT on telolength between before and after auto-HSCT showed shorting up to 1.0 kb. Moreover, comparison between mere length in children. We found that the telomere length of the HSCT patients was not significantly shorter than that donors and recipients in allo-HSCT revealed that telomeres of recipients were up to 1.0 kb shorter than those of age-matched putative normal controls, but telomere length was affected by donor age. of the donors. Patients who received allo-HSCT from donors older than 18 years had significantly shorter telomeres than those transplanted from donors under 18 years old (P Ͻ 0.05), indicating that donor age is an Patients and methods important factor for recipient's telomere length. These findings suggest that the effects which might be induced Patients by shortening of telomeres in recipients are within the Thirty-one children who underwent HSCT from 1983 to biologically tolerable range. However, if hematopoietic 1996 at Jikei University Hospital were studied. Two stem cells from elderly donors are transplanted into patients were treated with autologous bone marrow transyounger patients, the telomere length may become too plantation (auto-BMT), 11 patients received autologous short for acceptable lifetime risks of genetic instability peripheral blood stem cell transplantation (auto-PBSCT), in the recipient.and 18 patients underwent allogenic bone marrow transKeywords: hematopoietic stem cell transplantation; plantation (allo-BMT). No T cell-depleted stem cells were children; telomere length; chromosomal instability transplanted. The conversion to donor blood type was confirmed in allo-HSCTs by studying one or two of the following factors: the sex chromosome, the types of red blood Telomeres are special protein/DNA structures that cap the cells, and the types of HLA. The clinical characteristics of ends of linear eukaryotic chromosomes, preventing end-tothe patients are listed in Tables 1 and 2. The follow-up perend fusion and exonucleotic degradation.

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

“…Evidence for accelerated telomere shortening after haematopoietic stem cell transplantations was found in a number of studies (Shapiro et al, 1996;Notaro et al, 1997;Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999;Akiyama et al, 2000). Most data were derived from paediatric patients with haematological malignancies, and frequently mean TRF lengths after therapy were compared to mean TRF lengths of age-matched controls.…”

“…Most data were derived from paediatric patients with haematological malignancies, and frequently mean TRF lengths after therapy were compared to mean TRF lengths of age-matched controls. However, mean TRF length of nucleated blood cells has been shown to be widely variable between these controls (Notaro et al, 1997;Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999). Additionally, samples were drawn at a wide range of time after PBSCT, ranging from 1.6 months to over 10 years (Akiyama et al, 1998;Wynn et al, 1999).…”

“…However, mean TRF length of nucleated blood cells has been shown to be widely variable between these controls (Notaro et al, 1997;Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999). Additionally, samples were drawn at a wide range of time after PBSCT, ranging from 1.6 months to over 10 years (Akiyama et al, 1998;Wynn et al, 1999). Finally, as TRF dynamics were shown to be different in the various stages of life (Zeichner et al, 1999), predictive value for the adult setting may not automatically be assumed from these paediatric data.…”

“…On the X-axis blood sampling times t 0 (prior to chemotherapy), t 1 (5 months after chemotherapy) and t 2 (9 months after chemotherapy) are indicated. On the Y-axis, the following values are indicated with mean + SD: (A) leukocytes (10 9 1 -1 ); (B) platelets (10 9 1 -1 ); (C) haemoglobin (mmol 1 -1 ) and (D) MCV (fl) (Akiyama et al, 1998;Ball et al, 1998;Wynn et al, 1998;Lee et al, 1999). As shown in Figure 2, TRF length decreased in 9 patients of each group when t 0 and t 1 samples were compared, and 4 patients from the standard-and 5 patients from the high-dose group showed a TRF length increase (mean ∆ TRF length of both groups: -0.2 kb, SD 0.6; range ∆ TRF length: standard-dose group: +0.4 to -2.2 kb; high-dose group +0.8 to -1.1 kb).…”

In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency

“…In particular, aging of the newly differentiating progeny has been suggested as a potential side effect after BMT, even if this point is still debated. 18,39,40 In this regard, it has been hypothesized that cell senescence may be associated with the rapid expansion of engrafting HSCs aimed to repopulate the BM niches emptied by the conditioning regimen. Because during the gene transfer protocol procedures HSCs are manipulated in vitro and exposed to cytokines, this may increase the risk of premature senescence seen after standard BMT.…”