Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

Abstract

Telomerase activity and telomere length in mononuclear cells proliferation of lymphoid or myeloid precursors with arrested (MNCs) and granulocytes from peripheral blood (PB) and bone maturation. 1 In this disorder, the leukemic clone expands in marrow (BM) specimens were studied in pediatric acute leukethe bone marrow (BM), interferes with normal hematopoiesis mia (ALL, n = 15; AML, n = 1) and pediatric solid tumor (ST) and eventually, non-hematopoietic tissues are infiltrated. patients (n = 9) at diagnosis, during and after chemotherapy. In Acute lymphocytic leukemia (ALL) was one of the first maligfour ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were ananancies reported to respond to chemotherapy and is curable that can synthesize telomeric repeats onto chromosomes. [3][4][5][6] telomere loss in granulocytes as compared to MNCs was more Recently, borderline telomerase activity has been detected in pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consisthuman primitive hematopoietic cells and in stimulated lymently and highly upregulated in BM and PB specimens in leukephocytes which increased significantly with cytokine-induced mia, decreased after induction therapy, and correlated with ex vivo expansion. 7-10 However, in most other normal remission. BM specimens in leukemia had higher telomerase somatic cells, telomerase has not been detected, and conseactivity, probably due to the greater leukemic burden than in quently telomere shortening may be anticipated after a limited PB. Telomeres were significantly longer in children than in number of population doublings. [11][12][13] In contrast, spon- progressive telomere length shortening in the absence of telo-

Telomeres and telomerase in hematologic neoplasia

“…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). The expression of hTERT mRNA closely with telomerase activity measured by TRAP assay (Xu et al, 1998;Ohyashiki et al, 2001).…”

“…It is likely that the leukemia-derived stem cells express increasing levels of telomerase activity with an increasing fraction of cycling leukemia cells. The level of telomerase activity decreases to normal levels at the remission state and tends to be higher at the relapse phase (Tatematsu et al, 1996;Ohyashiki et al, 1997a, Engelhardt et al, 2000. Patients with high levels of telomerase activity show signi®cantly poorer prognosis compared to those with low telomerase activity (Ohyashiki et al, 1997a), indicating that telomerase activity may be a prognostic factor in acute leukemias.…”

Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients

“…21 Telomeres are shorter in the lymphocytes of patients who have been treated with chemotherapy, than in normal, agematched controls. 22,23 These prematurely shortened telomeres may be a result of the extra cell divisions this tissue must undergo to overcome the toxic effects of chemotherapy. This hypothesis is supported by studies that have documented accelerated telomere shortening in patients who have undergone high-dose chemotherapy with allogeneic bone marrow transplant.…”

Telomere dysfunction: multiple paths to the same end

“…Tumor cells, which likely undergo more cell divisions than their normal cellular counterparts, often possess shortened telomeres (de Lange et al, 1990;Engelhardt et al, 1997Engelhardt et al, , 1998Hastie et al, 1990). The observation that 90% of tumors exhibit telomerase activity (Shay and Bacchetti, 1997) suggests that tumor cells preferentially utilize telomerase to maintain telomeres and thus retain their proliferative potential.…”