Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells

  • Authors:
    • Oussama A. Saleh
    • William L. Blalock
    • Carla Burrows
    • Linda S. Steelman
    • Parul D. Doshi
    • John P. McKearn
    • James A. McCubrey
  • View Affiliations

  • Published online on: October 1, 2002     https://doi.org/10.3892/ijmm.10.4.385
  • Pages: 385-394
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Repopulating hematopoietic cell compartments after myeloablative chemotherapy remains a key factor in a successful chemotherapy program. Modified and chimeric cytokines have been developed to help reduce inflammation, fever and hospitalization time for patients. A chimeric cytokine, progenipoietin-1 (ProGP-1), containing the G-CSF and FL receptor agonists binds both the G-CSF receptor and FLT-3. It also stimulates the growth of dendritic cells, which play an important role in immunotherapy. While in vivo effects of ProGP-1 are well described, the mechanisms by which it stimulates growth are not well understood. We have investigated the effects of ProGP-1 on prevention of apoptosis in the human hematopoietic cell line OCI-AML.5. ProGP-1 promoted cellular proliferation better than G-CSF or FL separately but stimulated proliferation similar to their co-addition as demonstrated by growth curves and [3H]-thymidine incorporation. ProGP-1 prevented apoptosis to a greater degree than G-CSF or FL alone as determined by annexin V/propidium iodide binding and TUNEL assays. ProGP-1 promoted maintenance of the mitochondrial membrane potential better than G-CSF or FL alone. In addition, Pro-GP 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 data indicate that ProGP-1 promotes the proliferation and prevents the apoptosis of human hematopoietic cells better than FL or G-CSF alone, and to a similar extent as their co-addition. Thus, ProGP-1 can be used to repopulate certain hematopoietic cells as a single entity rather than the introduction of two different cytokines.

Related Articles

Journal Cover

October 2002
Volume 10 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Saleh OA, Blalock WL, Burrows C, Steelman LS, Doshi PD, McKearn JP and McCubrey JA: Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells. Int J Mol Med 10: 385-394, 2002
APA
Saleh, O.A., Blalock, W.L., Burrows, C., Steelman, L.S., Doshi, P.D., McKearn, J.P., & McCubrey, J.A. (2002). Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells. International Journal of Molecular Medicine, 10, 385-394. https://doi.org/10.3892/ijmm.10.4.385
MLA
Saleh, O. A., Blalock, W. L., Burrows, C., Steelman, L. S., Doshi, P. D., McKearn, J. P., McCubrey, J. A."Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells". International Journal of Molecular Medicine 10.4 (2002): 385-394.
Chicago
Saleh, O. A., Blalock, W. L., Burrows, C., Steelman, L. S., Doshi, P. D., McKearn, J. P., McCubrey, J. A."Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells". International Journal of Molecular Medicine 10, no. 4 (2002): 385-394. https://doi.org/10.3892/ijmm.10.4.385