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Cell Differentiation and Programmed Cell Death: A New Approach to Leukemia Therapy

  • Conference paper
Acute Leukemias V

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 37))

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Abstract

The establishment of a cell culture system for the clonal development of hematopoietic cells has made it possible to discover the proteins that regulate cell viability, growth and differentiation of different hematopoietic cell lineages and the molecular basis of normal and abnormal cell development in blood forming tissues. These regulators include cytokines now called colony stimulating factors and interleukins. Different cytokines can induce cell viability, multiplication and differentiation, and hematopoiesis is controlled by a network of cytokine interactions. Cytokines induce viability by inhibiting programmed cell death (apoptosis) including inhibition of apoptosis in leukemic cells treated with cytotoxic chemotherapy and irradiation therapy. Apoptosis and development of hematopoietic cells are also controlled by different genes including the tumor suppressor gene wild-type p53 and the oncogenes mutant p53, deregulated c-myc and bcl-2. Identification of the molecular controls of normal cell viability, growth and differentiation have made it possible to identify changes in the developmental program that result in leukemia. When normal cells have been changed into leukemic cells, the malignant phenotype can again be suppressed by inducing differentiation and apoptosis. Results on the suppression of malignancy in myeloid leukemia have shown that suppression of malignancy does not have to restore all the normal controls, and that genetic abnormalities which give rise to malignancy can be bypassed and their effects nullified by inducing differentiation and apoptosis. The results provide a new approach to therapy.

“The described cultures thus seem to offer a useful system for a quantitative kinetic approach to hematopoietic cell formation and for experimental studies on the mechanism and regulation of hematopoietic cell differentiation”[1].

In order to analyze the controls that regulate viability, multiplication and differentiation of normal hematopoietic cells to different cell lineages and the changes in these controls in disease, it is desirable and convenient to study the entire process in cell culture starting from single cells. Analysis of the molecular control of different types of hematopoietic cells therefore began with the development of a cell culture system for the cloning and clonal differentiation of different types of normal hematopoietic cells. This cell culture system was then used to discover a family of cytokines that regulate cell viability, multiplication and differentiation of different hematopoietic cell lineages, to analyze the origin of some hematological diseases, and to identify ways of treating these diseases with normal cytokines. I will mainly discuss cells of the myeloid cell lineages which have been used as a model system.

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Author information

Authors and Affiliations

  1. Department of Molecular Genetics and Virology, the Weizmann Institute of Science, 76100, Rehovot, Israel

    Leo Sachs

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  1. Leo Sachs
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Editor information

Editors and Affiliations

  1. Department of Internal Medicine, University of Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany

    W. Hiddemann  & W. Plunkett  & 

  2. Department of Internal Medicine, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    T. Büchner

  3. Department of Pediatric Oncology, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    J. Ritter

  4. Department of Internal Medicine, MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    B. Wörmann M.D., Ph.D.  & M. J. Keating M.D., B.S.  & 

  5. Koordinierungsstelle, Deutsche Krebsgesellschaft e.V., Thea-Bähnisch-Weg 12, 30657, Hannover, Germany

    U. Creutzig

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© 1996 Springer-Verlag Berlin Heidelberg

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Sachs, L. (1996). Cell Differentiation and Programmed Cell Death: A New Approach to Leukemia Therapy. In: Hiddemann, W., et al. Acute Leukemias V. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78907-6_1

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  • DOI: https://doi.org/10.1007/978-3-642-78907-6_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78909-0

  • Online ISBN: 978-3-642-78907-6

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