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  • 1
    Electronic Resource
    Electronic Resource
    Proliferation patterns in acute myeloid leukemia: leukemic clonogenic growth and in vivo cell cycle kinetics (1993)
    Springer
    Annals of hematology 66 (1993), S. 225-233 
    Details
    ISSN: 1432-0584
    Keywords: Flow cytometry ; Cell kinetics ; Iododeoxyuridine ; Clonogenic assay ; DNA synthesis time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a prospective study of 33 newly diagnosed patients with acute myeloid leukemia (AML), we analyzed the relationship of proliferation parameters with clinical parameters, response to induction therapy, and survival. The median follow-up was 26 months. The proliferative capacity of the leukemic progenitor cells was studied using colony-forming assays (number of colonyforming units, growth pattern, and spontaneous clonogenic growth capacity). The cell kinetic parameters of the bone marrow blasts were determined by in vivo labeling with iododeoxyuridine and subsequent flow cytometry: labeling index (LI), DNA synthesis time (Ts), potential doubling time. No or only weak relationships were observed between the experimental and clinical parameters such as age, sex, % blasts, white blood cell count, FAB subtype, cytogenetics, and % CD 34+ cells. This suggests that clonogenic growth and cell cycle kinetics of bone marrow blasts are independent cell biologic properties of AML. No association between the proliferation parameters and induction response rate was noticed. Analysis of the overall survival and event-free survival revealed trends to longer survival rates in patients with a belowmedian LI (≤7.6%) and below-median Ts value (≤14.3 h). These trends were more pronounced in the group of de novo AML (n=23), where the prolonged event-free survival in patients with below-median Ts reached statistical significance (p=0.02). None of the other parameters appeared significantly correlated with survival, although there was a trend to longer survival rates in patients who had no spontaneous clonogenic growth capacity (p=0.13). In conclusion, proliferation parameters in leukemic cells provide additional information on the cell biologic characteristics of AML, and these parameters may have prognostic value for response and duration of survival in AML.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01738470
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  • 2
    Electronic Resource
    Electronic Resource
    In vitro response of blasts to IL-3, GM-CSF, and G-CSF is different for individual AML patients: factors that stimulate leukemic clonogenic cells also enhance Ara-C cytotoxicity (1994)
    Springer
    Annals of hematology 68 (1994), S. 225-232 
    Details
    ISSN: 1432-0584
    Keywords: Ara-C ; AML ; CFU-L ; Hematopoietic growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vivo, growth factors are currently investigated for their capacity to trigger leukemic stem cells into cycle and thus overcome kinetic drug resistance. In this study, the susceptibility of leukemic clonogenic cells to individual growth factors was related to cytosine-arabinoside (Ara-C) sensitivity. The effects of interleukin-3 (IL-3), granulocyte-macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and combinations of these recombinant hematopoietic factors were tested on blast cells of nine acute myeloid leukemia (AML) patients. Growth factor responses were assessed in semi-solid clonogenic assay and in a 10-day liquid culture followed by clonogenic assay. Heterogeneity in growth factor response was observed in both test systems, resulting in a variable pattern for individual leukemias. In the majority of cases (six of nine) the response patterns in the semi-solid and liquid cultures were divergent. To test the Ara-C sensitivity, leukemic blasts were exposed in liquid to various concentrations of Ara-C in the absence and presence of preselected growth factors. After 10 days, the number of surviving leukemic colony-forming cells (CFU-L) was assessed. Exposure to Ara-C in the presence of optimal stimulatory factor(s) resulted in a 3- to 1000-fold increase of the Ara-C toxicity in seven patients. The Ara-C concentrations resulting in 50% inhibition of clonogenicity (ID50) were 0.48–123 x 10−8 M Ara-C in the absence of stimulatory growth factors, versus only 0.12–0.40 × 10−8 M Ara-C in the presence of these factors. In two patients, addition of one or more factors neither increased the number of CFU-L in liquid nor enhanced the Ara-C toxicity. Even in the absence of growth factors the ID50 values in these cases were as low as 0.20 and 0.28 × 10−8 M Ara-C and in the same range as the ID50 values observed with maximum growth factor stimulation in the other seven patients. These results indicate that Ara-C cytotoxicity can be enhanced by individually selected, clonogenic cell growth-promoting hematopoietic factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01737421
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    Paper (German National Licenses)
    Fulltext
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