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  • 1
    Online Resource
    Online Resource
    Limited Telomere Shortening in Hematopoietic Stem Cells after Transplantation
    Wiley ; 2001
    In:  Annals of the New York Academy of Sciences Vol. 938, No. 1 ( 2001-06), p. 1-8
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 938, No. 1 ( 2001-06), p. 1-8
    Abstract: A bstract : The number of cell divisions in hematopoietic stem cells (HSCs) following transplantation of bone marrow or mobilized peripheral blood into myelo‐ablated recipients is unknown. This number is expected to depend primarily on the number of transplanted stem cells, assuming that stem cells do not differ in engraftment potential and other functional properties. In a previous study, we found that the telomere length in circulating granulocytes in normal individuals shows a biphasic decline with age, most likely reflecting age‐related changes in the turnover of HSCs. In order to study HSCs' proliferation kinetics following stem cells transplantation, we analyzed the telomere length in donor‐derived nucleated blood cells in four HLA‐matched bone marrow transplant recipients relative to comparable cells from the sibling donors. In each case, the telomeres in granulocytes were shorter in the recipient than in the donor. This difference was established in the first year post transplantation and did not change after that. The telomere length in naïve and memory T cells showed marked differences after transplantation, complicating the interpretation of telomere length data using unseparated nucleated blood cells. Interestingly, the telomere length in naïve T cells that were first observed six months post transplantation was very similar in donor and recipient pairs. Our observations are compatible with a limited number of additional cell divisions in stem cell populations after bone marrow transplantations and support the idea that different populations of stem cells contribute to short‐term myeloid and long‐term lympho‐myeloid hematopoiesis.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.2001.938.issue-1
    DOI: 10.1111/j.1749-6632.2001.tb03568.x
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2001
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  • 2
    Online Resource
    Online Resource
    Telomere Length Dynamics in Normal Individuals and in Patients with Hematopoietic Stem Cell‐Associated Disorders
    Wiley ; 2001
    In:  Annals of the New York Academy of Sciences Vol. 938, No. 1 ( 2001-06), p. 293-304
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 938, No. 1 ( 2001-06), p. 293-304
    Abstract: A bstract : The telomere length in nucleated peripheral blood (PB) cells indirectly reflects the mitotic history of their precursors: the hematopoietic stem cells (HSCs). The average length of telomeres in PB leukocytes can be measured using fluorescence in situ hybridization and flow cytometry (flow FISH). We previously used flow FISH to characterize the age‐related turnover of HSCs in healthy individuals. In this review, we describe results of recent flow FISH studies in patients with selected hematopoietic stem cell‐associated disorders: chronic myelogeneous leukemia (CML) and several bone marrow failure syndromes. CML is characterized by a marked expansion of myeloid Philadelphia chromosome positive (Ph+) cells. Nevertheless, nonmalignant (Ph−) HSCs typically coexist in the bone marrow of CML patients. We analyzed the telomere length in 〉 150 peripheral blood leukocytes (PBLs) and bone marrow samples of patients with CML as well as samples of Ph‐ T‐lymphocytes. Compared to normal controls, the overall telomere fluorescence in PBLs of patients with CML was significantly reduced. However, no telomere shortening was observed in Ph‐ T‐lymphocytes. Patients in late chronic phase (CP) had significantly shorter telomeres than those assessed earlier in CP. Our data suggest that progressive telomere shortening is correlated with disease progression in CML. Within the group of patients with bone marrow failure syndromes, we only found significantly shortened telomeres (compared to age‐adjusted controls) in granulocytes from patients with aplastic anemia (AA). Strikingly, the telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy (recAA) did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia (sAANR) showed marked and significant telomere shortening compared to healthy donors and patients with recAA. Furthermore, an inverse correlation between age‐adjusted telomere length and peripheral blood counts was found in support of a model in which the degree of cytopenia and the amount of telomere shortening are correlated. These results support the concept of extensive proliferation of HSCs in subgroups of AA patients and suggest a potential use of telomere‐length measurements as a prognostic tool in this group of disorders as well.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.2001.938.issue-1
    DOI: 10.1111/j.1749-6632.2001.tb03598.x
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2001
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    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Asymmetric Cell Divisions in Hematopoietic Stem Cells
    Wiley ; 1999
    In:  Annals of the New York Academy of Sciences Vol. 872, No. 1 ( 1999-04), p. 265-273
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 872, No. 1 ( 1999-04), p. 265-273
    Abstract: A bstract : In order to study cell kinetics involved in long‐term hematopoiesis, we studied single sorted candidate hematopoietic stem cells (HSC) from fetal liver cultured in the presence of a mixture of stimulatory cytokines. After 8‐10 days in culture, the number of cells varied from less than a hundred to more than ten thousand cells. Single cells in slowly growing colonies were recloned upon reaching a 100‐200‐cell stage. Strikingly, the number of cells in subclones varied widely again. These results are indicative of asymmetric divisions in primitive hematopoietic cells in which the proliferative potential and cell cycle properties are unevenly distributed among daughter cells. The continuous generation of heterogeneity in cell cycle properties among the clonal progeny of HSC appears a relevant mechanism to maintain long‐term maintenance of hematopoiesis in vitro and in vivo.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.1999.872.issue-1
    DOI: 10.1111/j.1749-6632.1999.tb08471.x
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 1999
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    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Normalization of Previously Shortened Telomere Length under Treatment with Imatinib Argues against a Preexisting Telomere Length Deficit in Normal Hematopoietic Stem Cells from Patients with Chronic Myeloid Leukemia
    Wiley ; 2003
    In:  Annals of the New York Academy of Sciences Vol. 996, No. 1 ( 2003-05), p. 26-38
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 996, No. 1 ( 2003-05), p. 26-38
    Abstract: A bstract : Telomeres are composed of TTAGGG repeats and associated proteins. In somatic cells, telomere repeats are lost with each cell division, eventually leading to genetic instability and cellular senescence. In previous studies, we described substantial and disease stage‐specific telomere shortening in peripheral blood (PB) leukocytes from patients with chronic myeloid leukemia (CML). Here, we sought to determine whether age‐adjusted telomere length in PB granulocytes (deltaTEL gran ) is associated with response to treatment with the selective tyrosine kinase inhibitor imatinib. A total of 517 samples from 206 patients in chronic phase (CP), accelerated phase (AP), and blast crisis (BC) before and up to 706 days after initiation of imatinib therapy (median: 144 days) were analyzed by quantitative fluorescence in situ hybridization of interphase cells in suspension (Flow‐FISH); telomere fluorescence was expressed in molecular equivalents of soluble fluorochrome units (MESF). Telomere length in samples from start of treatment up to day 144 was significantly shorter (mean ± SE; −1.5 ± 0.3 kMESF) compared to samples from patients treated for more than 144 days (−0.8 ± 0.3 kMESF, p = 0.035 ). In patients with repeated measurements, a significant increase in telomere length under treatment was observed. Median telomere length in major remission was found to be significantly longer compared to patients without response to treatment measured either by cytogenetics ( n = 246 , p 〈 0.05 ), interphase FISH ( n = 204 , p = 0.002 ), or quantitative RT‐PCR ( n = 371 , p 〈 0.05 ). In conclusion, the increase in telomere length under treatment with imatinib reflects a shift from Ph+ to Ph− cells in the PB of patients with CML.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.2003.996.issue-1
    DOI: 10.1111/j.1749-6632.2003.tb03229.x
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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    SSG: 11
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Telomere Length Dynamics in Normal and Malignant Hematopoiesis
    Mary Ann Liebert Inc ; 2000
    In:  Journal of Anti-Aging Medicine Vol. 3, No. 4 ( 2000-01), p. 397-409
    Details
    In: Journal of Anti-Aging Medicine, Mary Ann Liebert Inc, Vol. 3, No. 4 ( 2000-01), p. 397-409
    Type of Medium: Online Resource
    ISSN: 1094-5458
    URL: Article
    DOI: 10.1089/rej.1.2000.3.397
    Language: English
    Publisher: Mary Ann Liebert Inc
    Publication Date: 2000
    detail.hit.zdb_id: 2155984-3
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