Telomere dynamics in childhood leukemia and solid tumors: a follow-up study.
Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childhood cancer. To define the long-term consequences of pediatric cancer treatment on hematopoietic cell telomere length, we undertook a prospective 4-year follow-up study of a 61-patient cohort of pediatric malignancies in a community-based setting. We found that mononuclear cells (MNC) and granulocytes of children with standard-risk acute lymphoblastic leukemia (ALL) suffered minimal telomere shortening throughout therapy (less than 1 kbp; average follow-up, 20 months), while those of children with solid tumors showed greater and more heterogenous telomere attrition (0.5-2.8 kbp, average follow-up, 9 months). In addition, we evaluated the role of telomerase, the enzyme commonly up-regulated in pediatric leukemic and solid tumor cells for telomere length maintenance, as a disease marker. Serial determinations of telomerase in MNC were useful to confirm disease remission in leukemia, but play no role in the follow-up of children with solid tumors.
Franco
S
S
James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Ozkaynak
M F
MF
Sandoval
C
C
Tugal
O
O
Jayabose
S
S
Engelhardt
M
M
Moore
M A S
MA
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D005500:Follow-Up Studies; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D015183:Restriction Mapping; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
D017931:DNA Primers; D019098:Telomerase