Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: Possible sites for intervention with anti-neoplastic drugs

W. L. Blalock, C. Weinstein-Oppenheimer, F. Chang, P. E. Hoyle, X. Y. Wang, P. A. Algate, R. A. Franklin, S. M. Oberhaus, L. S. Steelman, J. A. McCubrey

Research output: Contribution to journalArticle

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Abstract

Over the past decade, there has been an exponential increase in our knowledge of how cytokines regulate signal transduction, cell cycle progression, differentiation and apoptosis. Research has focused on different biochemical and genetic aspects of these processes. Initially, cytokines were identified by clonogenic assays and purified by biochemical techniques. This soon led to the molecular cloning of the genes encoding the cytokines and their cognate receptors. Determining the structure and regulation of these genes in normal and malignant hematopoietic cells has furthered our understanding of neoplastic transformation. Furthermore, this has allowed the design of modified cytokines which are able to stimulate multiple receptors and be more effective in stimulating the repopulation of hematopoietic cells after myelosuppressive chemotherapy. The mechanisms by which cytokines transduce their regulatory signals have been evaluated by identifying the involvement of specific protein kinase cascades and their downstream transcription factor targets. The effects of cytokines on cell cycle regulatory molecules, which either promote or arrest cell cycle progression, have been more recently examined. In addition, the mechanisms by which cytokines regulate apoptotic proteins, which mediate survival vs death, are being elucidated. Identification and characterization of these complex, interconnected pathways has expanded our knowledge of leukemogenesis substantially. This information has the potential to guide the development of therapeutic drugs designed to target key intermediates in these pathways and effectively treat patients with leukemias and lymphomas. This review focuses on the current understanding of how hematopoietic cytokines such as IL-3, as well as its cognate receptor, are expressed and the mechanisms by which they transmit their growth regulatory signals. The effects of aberrant regulation of these molecules on signal transduction, cell cycle regulatory and apoptotic pathways in transformed hematopoietic cells are discussed. Finally, anti-neoplastic drugs that target crucial constituents in these pathways are evaluated.

Original languageEnglish
Pages (from-to)1109-1166
Number of pages58
JournalLeukemia
Volume13
Issue number8
Publication statusPublished - 1999

Fingerprint

Interleukin-3
Signal Transduction
Cell Cycle
Cytokines
Pharmaceutical Preparations
Genetic Phenomena
Molecular Cloning
Cell Cycle Checkpoints
Protein Kinases
Genes
Molecular Biology
Lymphoma
Leukemia
Transcription Factors
Apoptosis
Drug Therapy
Survival
Growth
Research

Keywords

  • Anti-neoplastic drugs
  • Apoptosis
  • Cytokines
  • Oncogenes
  • Signal transduction

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Blalock, W. L., Weinstein-Oppenheimer, C., Chang, F., Hoyle, P. E., Wang, X. Y., Algate, P. A., ... McCubrey, J. A. (1999). Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: Possible sites for intervention with anti-neoplastic drugs. Leukemia, 13(8), 1109-1166.

Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells : Possible sites for intervention with anti-neoplastic drugs. / Blalock, W. L.; Weinstein-Oppenheimer, C.; Chang, F.; Hoyle, P. E.; Wang, X. Y.; Algate, P. A.; Franklin, R. A.; Oberhaus, S. M.; Steelman, L. S.; McCubrey, J. A.

In: Leukemia, Vol. 13, No. 8, 1999, p. 1109-1166.

Research output: Contribution to journalArticle

Blalock, WL, Weinstein-Oppenheimer, C, Chang, F, Hoyle, PE, Wang, XY, Algate, PA, Franklin, RA, Oberhaus, SM, Steelman, LS & McCubrey, JA 1999, 'Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: Possible sites for intervention with anti-neoplastic drugs', Leukemia, vol. 13, no. 8, pp. 1109-1166.
Blalock, W. L. ; Weinstein-Oppenheimer, C. ; Chang, F. ; Hoyle, P. E. ; Wang, X. Y. ; Algate, P. A. ; Franklin, R. A. ; Oberhaus, S. M. ; Steelman, L. S. ; McCubrey, J. A. / Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells : Possible sites for intervention with anti-neoplastic drugs. In: Leukemia. 1999 ; Vol. 13, No. 8. pp. 1109-1166.
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