REGULATION OF MYELOPOIESIS: SUPPRESSOR FACTOR SYNERGISM

Project: Research project

Description

The control of proliferation of hematopoietic stem and progenitor cells in
vivo is most likely the end result of the production and action of
growth-stimulating and growth-suppressing molecules. We have defined and
characterized the influence of purified natural and recombinant molecules
such as acidic isoferritins, the interferons gamma, alpha and beta, the E
type prostaglandins, and tumor necrosis factor on normal and abnormal
hematopoiesis. Of much interest to us, and potentially of great importance
and relevance to an understanding of the physiological regulation of
hematopoietic cell proliferation in vivo and of abnormalities in this
regulation during leukemia and related blood disorders is the recent
findings by us and others that certain molecules can synergise with each
other in vitro so that the effects noted are much greater than additive.
We propose to investigate the phenomenon of synergism between molecules in
vitro and in vivo. Our aims are to evaluate further and more precisely the
actions and interactions alone and in combination of well-characterized and
purified natural or recombinant acidic isoferritins, interferons-gamma and
-alpha, prostaglandin E1 or E2 and tumor necrosis factor on the growth in
vitro of fresh primary normal human and murine myeloid cells, on cells from
patients with leukemia and related disorders, and on established human
myeloid leukemia cell lines in vitro. Our goal is to study these
molecule-cell interactions using pure molecules and purified populations of
target cells, isolated by biophysical and immunological procedures, in the
presence and absence of serum. Studies in vitro will include an analysis
of the activity of these molecules using colony forming cell assays
(CFU-GM, BFU-E, CFU-GEMM, S-cells), the receptor-binding capacity of these
molecules, and effects of these molecules on the expression of
proto-oncogenes. We also propose to evaluate the separate and combined
actions of these molecules in vivo in mice undergoing rebound myelopoiesis,
in untreated mice, and in mice infected with the Friend Viruis Complex. We
believe that the studies proposed will increase our understanding of the
relevance of these molecules and the concept of synergism as it applies to
normal and abnormal regulation.
StatusFinished
Effective start/end date7/1/836/30/91

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Myelopoiesis
Leukemia
Hematopoietic Stem Cells
Interferon-gamma
Interferon-alpha
Tumor Necrosis Factor-alpha
Erythroid Precursor Cells
Myeloid Progenitor Cells
Alprostadil
Interferon-beta
Myeloid Cells
Growth
Oncogenes
Dinoprostone
Cell Communication
Prostaglandins
Histocompatibility Antigens Class II
Cell Proliferation
HLA-DR Antigens
Cell Line

ASJC

  • Medicine(all)