Telomeric DNA in normal and leukemic blood cells.

Abstract

We studied telomeric DNA in leukemic cells as well as in normal T cells, B cells, monocytes, polymorphonuclear leukocytes, and bone marrow hematopoietic progenitor cells. No marked differences were observed in the sizes of the telomeric repeats in the various populations of normal blood cells obtained from donors in their twenties to sixties, and the telomere length ranged between 8.5 and 9.0 kb. The leukemic cells of 12 patients with acute leukemia (seven with myeloid and five with lymphoid leukemia) showed a variable reduction in the length of telomeric DNA, ranging from 2.7 to 6.4 kb. The average telomere length was 4.8 and 4.7 kb in myeloid and lymphoid leukemia, respectively, while the telomere length in peripheral blood mononuclear cells obtained from the same patients during complete remission was 8.5 and 7.9 kb, respectively. When the same Southern blots were hybridized with Alu or alphoid sequences, no marked changes in the sizes of the repetitive DNA sequences were observed, indicating that the DNA abnormality in the leukemic cells was specific to the telomere region. Investigation of telomeric DNA changes may be helpful in determining the biological properties of leukemic cells.

Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells

“…Our observations dispel a commonly held assumption regarding the timing of telomerase dysregulation in the leukemogenic process. In AML blasts, telomeres are generally shorter than those of normal cells (21,22), which has been thought to reflect up-regulation of telomerase expression only in the later stages of leukemogenesis after telomeres have shortened because of leukemic proliferation. Our finding of dissociation between telomerase activity and telomere length maintenance in hematopoietic cells indicates that telomerase up-regulation can be an earlier step in the leukemogenic program.…”

“…Solid tumors arising in telomerase-negative tissues typically circumvent this barrier by inactivation of checkpoints triggered by loss of telomere function and eventually by activation of telomerase expression. Although acute myelogenous leukemia (AML) is thought to originate in telomerase-expressing HSC (19,20), telomeres in AML blasts are generally shorter than those in normal cells (21,22), suggesting that as in normal HSC, telomerase in leukemic stem cells does not prevent proliferationassociated loss of telomeric DNA. Nevertheless, high levels of telomerase activity are present in Ͼ70% of AML cases (23).…”

Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation

“…16 However, recent precise studies demonstrated a significant difference between T cells and neutrophils. Moreover, memory T cells are shown to have shorter telomeres than those of naive T cells.…”

Telomeres and telomerase in hematologic neoplasia

“…After quantitative system of telomerase activity was established, approximately 75% of the patients with acute leukemia showed elevated levels of telomerase activity. Telomere length was generally shortened (Takeuchi et al, 1994;Yamada et al, 1995;Ohyashiki et al, 1997a). A high level of telomerase activity (more than 10-fold compared to normal hematopoietic cells) was noted in both AML and ALL (Counter et al, 1995;Broccoli et al, 1995;Zhang et al, 1996;Ohyashiki et al, 1997a;Li et al, 2000;Engelhardt et al, 2000).…”