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Enhanced ability of danispletim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells

Leukemia, ISSN: 0887-6924, Vol: 15, Issue: 8, Page: 1203-1216
2001
  • 11
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  • 11
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Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    11
    • Citation Indexes
      11
  • Captures
    11

Article Description

Modified and chimeric cytokines have been developed to aid in the recovery of hematopoietic precursor cells after myeloablative chemotherapy. The interleukin-3 (IL-3) receptor agonist, daniplestim, binds to the IL-3 receptor-α subunit with 60-fold greater affinity and induces cell proliferation and colony-forming unit formation 10- to 22-fold better than native IL-3. A chimeric cytokine, myelopoietin-1, composed of daniplestim and a G-CSF receptor agonist binds both the IL-3 and G-CSF receptors. While the in vivo effects of daniplestim and myelopoietin-1 are well described, the mechanisms by which they stimulate growth are not well understood. We have investigated the effects of daniplestim and myelopoietin-1 on the prevention of apoptosis in two human hematopoietic cell lines, OCI-AML.5 and AML 193. Daniplestim and myelopoietin-1 prevented apoptosis to a greater degree than native recombinant IL-3 or G-CSF as determined by annexin V/propidium iodide binding and TUNEL assays. Daniplestim and myelopoietin-1 promoted the maintenance of the mitochondrial membrane potential better than native IL-3 or G-CSF. These cytokines promoted a lower redox potential as higher levels of free radicals were detected after cytokine treatment than in cytokine-deprived cells implying increased respiration. These results indicate that daniplestim and myelopoietin-1 are able to prevent apoptosis in hematopoietic cells more effectively than native IL-3 and G-CSF. These effects of daniplestim and myelopoietin-1 may contribute to their effective ability to repopulate hematopoietic precursor cells after chemotherapy.

Bibliographic Details

J. A. McCubrey; W. L. Blalock; O. Saleh; M. Pearce; C. Burrows; L. S. Steelman; J. T. Lee; R. A. Franklin; S. M. Oberhaus; P. W. Moye; P. D. Doshi; J. P. McKearn

Springer Science and Business Media LLC

Medicine; Biochemistry, Genetics and Molecular Biology

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