Telomere loss in Philadelphia-negative hematopoiesis after successful treatment of chronic myeloid leukemia: evidence for premature aging of the myeloid compartment.
Telomere shortening, a well-known marker of aging and cellular stress, occurs under several conditions in the hematopoietic compartment, including aplastic anemia and following iatrogenic noxae. We decided to verify whether pathological telomere erosion also arises in restored Philadelphia-negative (Ph-negative) hematopoiesis following successful treatment of chronic myeloid leukemia (CML). Eighty-one CML patients in complete cytogenetic remission were compared to 76 age-matched healthy subjects. Myeloid cells of CML patients had shorter telomeres than controls (6521 bp vs 7233 bp, p<0.001). This difference was specific for the myeloid compartment, since it was not observed in lymphoid cells (6774 bp vs 6909 bp, p=0.620). Acquired Ph-negative cytogenetic abnormalities (p=0.010), lack of complete molecular remission (p=0.016) and age (p=0.013) were independent predictors of telomere shortening. Telomere dynamics were assessed over a median follow-up period of 22 months. We documented accelerated non-physiological ongoing telomere shortening in 17/59 CML patients (28%). Patients experiencing grade 2-4 hematological toxicity, during CML remission possessed significantly shorter telomeres compared to those lacking toxicity (p=0.005 for any toxicity, p=0.007 for anemia). CML patients suffer from significant and often ongoing telomere stress resulting in premature and selective aging of the myeloid compartment which might have long-term consequences on function and integrity of Ph-negative hematopoiesis.
Division of Hematology, University of Turin, A.O.U. San Giovanni Battista, Turin, Italy.
Chiara
C
Lobetti-Bodoni
Dario
D
Ferrero
Elisa
E
Genuardi
Roberto
R
Passera
Elisa
E
Bernocco
Daniela
D
Sia
Giovanni
G
Grignani
Elena
E
Crisà
Luigia
L
Monitillo
Alberto
A
Rocci
Daniela
D
Drandi
Valentina
V
Giai
Manuela
M
Zanni
Michela
M
Boi
Gianluca
G
Isaia
Daniela
D
Barbero
Monia
M
Lunghi
Elisabetta
E
Abruzzese
Franca
F
Radaelli
Massimo
M
Pini
Patrizia
P
Pregno
Carmelo
C
Carlo-Stella
Gianluca
G
Gaidano
Mario
M
Boccadoro
Marco
M
Ladetto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019588:Aging, Premature / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D005500:Follow-Up Studies; D006410:Hematopoiesis; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D016615:Telomere / Q000378:metabolism*