Exisulind induces apoptosis in advanced myelodysplastic syndrome (MDS) and acute myeloid leukaemia/MDS

Authors

  • Akos Czibere,

    1. Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany
    2. Genomics Center of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston/MA, USA
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    • *

      Both authors contributed equally to this work.

  • Wolf C. Prall,

    1. Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany
    2. Genomics Center of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston/MA, USA
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    • *

      Both authors contributed equally to this work.

  • Luiz F. Zerbini,

    1. Genomics Center of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston/MA, USA
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  • Markus Jäger,

    1. Department of Orthopaedic Surgery, Heinrich Heine-University, Düsseldorf, Germany
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  • Guido Kobbe,

    1. Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany
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  • Sabine Knipp,

    1. Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany
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  • Towia A. Libermann,

    1. Genomics Center of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston/MA, USA
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  • Rainer Haas,

    1. Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany
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  • Manuel Aivado

    1. Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany
    2. Genomics Center of the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston/MA, USA
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Akos Czibere, MD, Department of Haematology, Oncology, and Clinical Immunology, Heinrich Heine-University, Düsseldorf Moorenstr. 5, 40225 Düsseldorf, Germany. E-mail: aczibere@bidmc.harvard.edu

Summary

The influence of Exisulind on the viability and apoptosis of CD34+ stem cells from patients with advanced myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML)/MDS was investigated. In eight out of 10 patient samples Exisulind reduced the fraction of viable cells by inducing apoptosis. We found evidence that Exisulind-mediated apoptosis depends on c-Jun NH2-terminal kinase (JNK) activation. Addition of a specific JNK-inhibitor to Exisulind-treated advanced MDS and AML/MDS cells partly abrogated apoptosis. We propose that Exisulind is tested in clinical phase I/II trials for the treatment of advanced MDS and AML/MDS.

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