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

Oussama A. Saleh, William L. Blalock, Carla Burrows, Linda S. Steelman, Parul D. Doshi, John P. McKearn, James A. McCubrey

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)385-394
Number of pages10
JournalInternational Journal of Molecular Medicine
Volume10
Issue number4
Publication statusPublished - Oct 2002

ASJC Scopus subject areas

  • Genetics

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    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(4), 385-394.