Article (Scientific journals)
Telomere shortening correlates with leukemic stem cell burden at diagnosis of chronic myeloid leukemia.
Bouillon, Anne-Sophie; Ventura Ferreira, Monica S.; Awad, Shady Adnan et al.
2018In Blood Advances, 2 (13), p. 1572-1579
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Keywords :
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/drug therapy/genetics/metabolism; Male; Middle Aged; Protein Kinase Inhibitors/administration & dosage; Telomere Homeostasis
Abstract :
[en] Telomere length (TL) in peripheral blood (PB) cells of patients with chronic myeloid leukemia (CML) has been shown to correlate with disease stage, prognostic scores, response to therapy, and disease progression. However, due to considerable genetic interindividual variability, TL varies substantially between individuals, limiting its use as a robust prognostic marker in individual patients. Here, we compared TL of BCR-ABL(-), nonleukemic CD34(+)CD38(-) hematopoietic stem cells (HSC) in the bone marrow of CML patients at diagnosis to their individual BCR-ABL(+) leukemic stem cell (LSC) counterparts. We observed significantly accelerated telomere shortening in LSC compared with nonleukemic HSC. Interestingly, the degree of LSC telomere shortening was found to correlate significantly with the leukemic clone size. To validate the diagnostic value of nonleukemic cells as internal controls and to rule out effects of tyrosine kinase inhibitor (TKI) treatment on these nontarget cells, we prospectively assessed TL in 134 PB samples collected in deep molecular remission after TKI treatment within the EURO-SKI study (NCT01596114). Here, no significant telomere shortening was observed in granulocytes compared with an age-adjusted control cohort. In conclusion, this study provides proof of principle for accelerated telomere shortening in LSC as opposed to HSC in CML patients at diagnosis. The fact that the degree of telomere shortening correlates with leukemic clone's size supports the use of TL in leukemic cells as a prognostic parameter pending prospective validation. TL in nonleukemic myeloid cells seems unaffected even by long-term TKI treatment arguing against a reduction of telomere-mediated replicative reserve in normal hematopoiesis under TKI treatment.
Disciplines :
Hematology
Author, co-author :
Bouillon, Anne-Sophie ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'hématologie clinique
Ventura Ferreira, Monica S.
Awad, Shady Adnan
Richter, Johan
Hochhaus, Andreas
Kunzmann, Volker
Dengler, Jolanta
Janssen, Jeroen
Ossenkoppele, Gert
Westerweel, Peter E.
Te Boekhorst, Peter A. W.
Mahon, Francois-Xavier
Hjorth-Hansen, Henrik
Isfort, Susanne
Fioretos, Thoas
Hummel, Sebastian
Schemionek, Mirle
Wilop, Stefan
Koschmieder, Steffen
Saussele, Susanne
Mustjoki, Satu
Beier, Fabian
Brummendorf, Tim H.
More authors (13 more) Less
Language :
English
Title :
Telomere shortening correlates with leukemic stem cell burden at diagnosis of chronic myeloid leukemia.
Publication date :
2018
Journal title :
Blood Advances
ISSN :
2473-9529
eISSN :
2473-9537
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
Volume :
2
Issue :
13
Pages :
1572-1579
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2018 by The American Society of Hematology.
Available on ORBi :
since 22 April 2020

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