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Progressive Telomere Shortening in Aplastic Anemia
Sarah E. Ball,
Frances M. Gibson,
Siân Rizzo,
Jennifer A. Tooze,
Judith C.W. Marsh, and
Edward C. Gordon-Smith
From the Division of Haematology, Department of Cellular and
Molecular Sciences, St George's Hospital Medical School, London, UK.
Improved survival in aplastic anemia (AA) has shown a high incidence
of late clonal marrow disorders. To investigate whether accelerated
senescence of hematopoietic stem cells might underlie the
pathophysiology of myelodysplasia (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late complication of AA, we studied
mean telomere length (TRF) in peripheral blood leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with normal
controls. TRF lengths in the patient group were significantly shorter
for age than normals (P < .0001). Telomere shortening was
apparent in both granulocyte and mononuclear cell fractions, suggesting
loss at the level of the hematopoietic stem cell. In patients with
acquired AA with persistent cytopenias (n = 40), there was
significant correlation between telomere loss and disease duration
(r =  .685; P < .0001), equivalent to progressive
telomere erosion at 216 bp/yr, in addition to the normal age-related
loss. In patients who had achieved normal full blood counts (n = 20), the rate of telomere loss had apparently stabilised. There was no
apparent association between telomere loss and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less than 5.0 kb,
3 had acquired cytogenetic abnormalities, suggesting that telomere
erosion may be relevant to the pathogenesis of MDS in aplastic anemia.
Blood, Vol. 91 No. 10 (May 15), 1998:
pp. 3582-3592
© 1998 by The American Society of Hematology.
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110(5):
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12(21):
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[Full Text]
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|
|
|
|
|
|
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108(8):
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|
|
|
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106(4):
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|
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|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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104(13):
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|
|
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|
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|
|
|
|
|
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|
|
|
|
|
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|
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July 15, 2003;
102(2):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Theimer, L. D. Finger, L. Trantirek, and J. Feigon
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January 21, 2003;
100(2):
449 - 454.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M D Tischkowitz and S V Hodgson
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J. Med. Genet.,
January 1, 2003;
40(1):
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[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. U. WIEMANN, A. SATYANARAYANA, M. TSAHURIDU, H. L. TILLMANN, L. ZENDER, J. KLEMPNAUER, P. FLEMMING, S. FRANCO, M. A. BLASCO, M. P. MANNS, et al.
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16(9):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Thornley, R. Sutherland, R. Wynn, R. Nayar, L. Sung, G. Corpus, T. Kiss, J. Lipton, J. Doyle, F. Saunders, et al.
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April 1, 2002;
99(7):
2387 - 2396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Blood,
March 1, 2001;
97(5):
1274 - 1281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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February 15, 2001;
97(4):
895 - 900.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Koetz, E. Bryl, K. Spickschen, W. M. O'Fallon, J. J. Goronzy, and C. M. Weyand
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97(16):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Boultwood, A. Peniket, F. Watkins, P. Shepherd, P. McGale, S. Richards, C. Fidler, T. J. Littlewood, and J. S. Wainscoat
Telomere length shortening in chronic myelogenous leukemia is associated with reduced time to accelerated phase
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July 1, 2000;
96(1):
358 - 361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Rudolph, S. Chang, M. Millard, N. Schreiber-Agus, and R. A. DePinho
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Science,
February 18, 2000;
287(5456):
1253 - 1258.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Engelhardt, K. Mackenzie, P. Drullinsky, R. T. Silver, and M. A. S. Moore
Telomerase Activity and Telomere Length in Acute and Chronic Leukemia, Pre- and Post-ex Vivo Culture
Cancer Res.,
February 1, 2000;
60(3):
610 - 617.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. S. Young, J. L. Abkowitz, and L. Luzzatto
New Insights into the Pathophysiology of Acquired Cytopenias
Hematology,
January 1, 2000;
2000(1):
18 - 38.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Friedberg, D. Neuberg, R. M. Stone, E. Alyea, H. Jallow, A. LaCasce, P. M. Mauch, J. G. Gribben, J. Ritz, L. M. Nadler, et al.
Outcome in Patients With Myelodysplastic Syndrome After Autologous Bone Marrow Transplantation for Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
October 1, 1999;
17(10):
3128 - 3135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. S. Young
Acquired Aplastic Anemia
JAMA,
July 21, 1999;
282(3):
271 - 278.
[Full Text]
[PDF]
|
|
|
|
|
