Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia: Evidence for premature aging of the myeloid compartment

Lobetti-Bodoni, Chiara; Ferrero, Dario; Genuardi, Elisa; Passera, Roberto; Bernocco, Elisa; Sia, Daniela; Grignani, Giovanni; Crisà, Elena; Monitillo, Luigia; Rocci, Alberto; Drandi, Daniela; Giai, Valentina; Zanni, Manuela; Boi, Michela; Isaia, Gianluca; Barbero, Diego; Lunghi, Monia; Abruzzese, Elisabetta; Radaelli, Franca; Pini, Massimo; Pregno, Patrizia; Carlo‐Stella, Carmelo; Gaïdano, Gianluca; Boccadoro, Mario; Ladetto, Marco

doi:10.1016/j.mad.2012.05.007

Cited by 8 publications

(7 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the four remaining, three had recovery times well above the mean (57 to 73 days) after intensification three, and one never recovered. Similarly, telomere shortening in association with grade 2 to 4 hematologic toxicities was observed in those with chronic myeloid leukemia in remission, 26 suggesting a relationship between telomere shortening and therapy-associated cytopenias.…”

Section: Discussionmentioning

confidence: 93%

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group

Gerbing

Alonzo

Sung

et al. 2016

JCO

View full text Add to dashboard Cite

Purpose Suboptimal outcomes for children with acute myeloid leukemia (AML) necessitate maximally intensive therapy. Consequently, serious adverse events, such as prolonged periods of profound myelosuppression, contribute to AML treatment–related mortality. Telomeres, the repetitive DNA–protein structures at chromosome ends, influence cellular replicative capacity in that critically short telomeres can induce cell senescence or apoptosis. Our objective was to evaluate the impact of telomere length on duration of post-therapy neutropenia in a pediatric AML cohort. Patients and Methods Patients were diagnosed with de novo AML, enrolled in Children’s Oncology Group study AAML0531, and included those with (n = 53) and without (n = 62) significantly delayed neutrophil recovery after chemotherapy. We used quantitative polymerase chain reaction to measure telomere content (TC), a validated proxy for telomere length, from remission bone marrow samples obtained after the second induction chemotherapy course. Results Less TC was significantly associated with prolonged neutropenia after the fourth (P < .001) and fifth chemotherapy courses (P = .002). Cox regression adjusting for age at diagnosis confirmed that TC remained independently predictive of time to recovery of absolute neutrophil count for both the fourth and fifth courses (P = .002 and .009, respectively). DNA from patients was analyzed for germline mutations in four telomere maintenance genes associated with telomere biology disorders. Sequence analysis revealed no enrichment of rare or novel variants in the delayed recovery group. Conclusion Our results suggest that TC at end of AML induction is associated with hematopoietic reconstitution capacity independently of age and may identify those at highest risk for markedly delayed bone marrow recovery after AML therapy.

show abstract

Section: Discussionmentioning

confidence: 93%

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group

Gerbing

Alonzo

Sung

et al. 2016

JCO

View full text Add to dashboard Cite

show abstract

“… 45 Various cytotoxic drugs (cyclophosphamide, doxorubicin, azidothymidine, 5-fluorouracil) have been shown to induce senescence directly in tumours via DNA damage. 68 Many drugs act similarly, inducing ageing-related biological pathways. 66 …”

Section: Resultsmentioning

confidence: 99%

Biology of premature ageing in survivors of cancer

et al. 2017

View full text Add to dashboard Cite

Over 30 million cancer survivors exist worldwide. Survivors have an earlier onset and higher incidence of chronic comorbidities, including endocrinopathies, cardiac dysfunction, osteoporosis, pulmonary fibrosis, secondary cancers and frailty than the general population; however, the fundamental basis of these changes at the cellular level is unknown. An electronic search was performed on Embase, Medline In-Process & Other Non-Indexed Citations, and the Cochrane Central Register of Controlled Trials. Original articles addressing the cellular biology of ageing and/or the mechanisms of cancer therapies similar to ageing mechanisms were included, and references of these articles were reviewed for further search. We found multiple biological process of ageing at the cellular level and their association with cancer therapies, as well as with clinical effects. The direct effects of various chemotherapies and radiation on telomere length, senescent cells, epigenetic modifications and microRNA were found. We review the effects of cancer therapies on recognised hallmarks of ageing. Long-term comorbidities seen in cancer survivors mimic the phenotypes of ageing and likely result from the interaction between therapeutic exposures and the underlying biology of ageing. Long-term follow-up of cancer survivors and research on prevention strategies should be pursued to increase the length and quality of life among the growing population of cancer survivors.

show abstract

“…Ten of the studies were judged to be of overall moderate quality; one was judged to be of poor quality based on the criteria assessed (48). The types of hematological cancers investigated were chronic myeloid leukemia (CML) in four studies (40,44,46,47), non-Hodgkin lymphoma (NHL) in three studies (41,43,45), and acute promyelocytic leukemia (15), Hodgkin lymphoma (42), acute lymphocytic leukemia (ALL) (48), and lymphoma, not otherwise specified (13), in one study each.…”

Section: Hematological Malignancy Only Studiesmentioning

confidence: 99%

The Effect of Cancer Treatments on Telomere Length: A Systematic Review of the Literature

Gallicchio

Gadalla

Murphy

et al. 2018

JNCI: Journal of the National Cancer Institute

View full text Add to dashboard Cite

Background: It has been hypothesized that cancer treatments cause accelerated aging through a mechanism involving the shortening of telomeres. However, the effect of cancer treatments on telomere length is unclear. Methods: We systematically reviewed the epidemiological evidence evaluating the associations between cancer treatment and changes in telomere length. Searches were performed in PubMed for the period of January 1966 through November 2016 using the following search strategy: telomere AND (cancer OR tumor OR carcinoma OR neoplasm) AND (survivor OR patient). Data were extracted and the quality of studies was assessed. Results: A total of 25 studies were included in this review. Ten were solid cancer studies, 11 were hematological malignancy studies, and 4 included a mixed sample of both solid and hematological cancers. Three of the 10 solid tumor studies reported a statistically significant association between cancer treatment and telomere length shortening, and one reported longer telomere length after treatment. Among the hematological cancer studies, three showed statistically significant decreases in telomere length with treatment, and two showed elongation. When these studies were rated using quality criteria, most of the studies were judged to be of moderate quality. Conclusions: The findings from this review indicate that the effect of cancer treatment on telomere length may differ by cancer type and treatment as well as other factors. Definitive conclusions cannot be made based on the published literature, because sample sizes tended to be small; treatments, cancer types, and biospecimens were heterogenous; and the length of follow-up times differed greatly. REVIEW

show abstract

Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia: Evidence for premature aging of the myeloid compartment

Cited by 8 publications

References 71 publications

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group

Shorter Remission Telomere Length Predicts Delayed Neutrophil Recovery After Acute Myeloid Leukemia Therapy: A Report From the Children’s Oncology Group

Biology of premature ageing in survivors of cancer

The Effect of Cancer Treatments on Telomere Length: A Systematic Review of the Literature

Contact Info

Product

Resources

About