What Is Hemopoietic Growth Factor? Definition and What Research Reports

Definition

Hemopoietic growth factor (also spelled haemopoietic or hematopoietic growth factor, and often abbreviated HGF in the older hematology literature) is an umbrella term for secreted regulatory proteins that act on blood-forming cells in the bone marrow. The label covers a family rather than a single molecule: the colony-stimulating factors (including GM-CSF), interleukin-3 and related multi-lineage factors, and ligands such as Steel factor. Each acts by binding a specific receptor on the surface of a progenitor cell, and the term is used in the literature to describe any factor whose activity is measured by the survival, proliferation or colony formation of hemopoietic progenitors in culture. The abbreviation should not be confused with hepatocyte growth factor, which shares the same three letters in more recent papers.

What Class of Molecule Is It, and Where Does It Come From?

Hemopoietic growth factors are polypeptides — typically glycosylated proteins rather than short synthetic peptides — produced by accessory and stromal cells that surround developing blood cells. The classic sources described in the literature are lymphocytes, marrow stromal populations and certain leukemic cell lines. Researchers characterised hemopoietic growth factors produced by T cells and by the myelomonocytic leukemia line WEHI-3B, comparing their biochemical and biological properties in a 1985 report in Experimental Hematology. Separate work examined hemopoietic growth factor production by bone marrow adherent cells, the stromal population that forms the supportive layer in long-term marrow cultures, as described in a 1985 conference report.

Production is not confined to the marrow. A 1989 study mapped the tissue distribution of murine hemopoietic growth factor messenger RNA production, showing that transcripts for these factors could be detected across multiple mouse tissues rather than in a single organ (Journal of Cellular Physiology, 1989). Transformation of cells can also switch factor genes on: researchers reported the activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells (Experimental Hematology, 1988).

How the Term Is Used in Peptide and Hematology Research

In the research literature the phrase functions as a functional category, defined by assay rather than by structure. A protein earns the label if progenitor cells depend on it. That dependency is the basis of the classic factor-dependent cell line assay: a cell line is maintained in culture only while the factor is present, and withdrawal is used to study survival signalling. One 1989 study examined the interaction of serum and colony-stimulating factor in supporting the survival of a factor-dependent hemopoietic progenitor cell line, separating the contribution of serum components from that of the growth factor itself (Journal of Cellular Physiology, 1989).

The second common use of the term is in receptor biology. Because these factors signal through defined surface receptors, much of the literature is about how those receptors behave. A 1985 paper in Cell described hierarchical down-modulation of hemopoietic growth factor receptors, in which exposure to one factor reduced the surface availability of receptors for others in a ranked order (Cell, 1985). Downstream of the receptor, researchers reported that Steel factor stimulated the tyrosine phosphorylation of the proto-oncogene product p95vav in human hemopoietic cells, linking a hemopoietic growth factor to an intracellular signalling substrate (Journal of Biological Chemistry, 1992).

Terms Frequently Used Alongside It

What the Published Literature Reports

Three strands dominate the older literature. The first is regulation of factor activity. Researchers reported that ADP-ribosylation inhibitors inhibited hemopoietic growth factor-induced proliferation, implicating that biochemical pathway in the proliferative response (Blood, 1987). A companion line of work reported differential inhibition of hemopoietic growth factor activity by cytotoxins and interferon-gamma, indicating that factor activity could be opposed by other immune mediators rather than acting unopposed (Journal of Immunology, 1987).

The second strand is receptors and disease. A 1998 review in Leukemia Research examined hemopoietic growth factor receptor abnormalities in leukemia, situating altered receptor structure or expression within leukemic biology (Leukemia Research, 1998). Together with the earlier report of hierarchical receptor down-modulation (Cell, 1985), this literature treats the receptor, not only the ligand, as the regulated element.

The third strand is gene-level manipulation. Hemopoietic growth factor gene transfer was described as an experimental approach in a 1989 report in Transplantation Proceedings, and the consequences of constitutive expression were examined in whole animals in the transgenic work summarised below.

Effects Observed in Animal Models: What Studies Report

The most frequently cited in vivo observation for this class comes from a 1987 Cell paper in which transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) were reported to develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage (Cell, 1987). The study is routinely referenced as evidence that sustained, unregulated expression of a hemopoietic growth factor in an intact animal produced pathology rather than a simple increase in blood cell output. No human dosing information is drawn from these reports, and the verified literature summarised here does not establish dose ranges, schedules or safety margins for any species.

Comparable cautionary signals appear in vitro: inhibition of factor-induced proliferation by ADP-ribosylation inhibitors (PMID 2957001) and by cytotoxins and interferon-gamma (PMID 3112224) indicate that responses measured in culture depend heavily on what else is present in the system.

Limitations of This Entry

• Most of the primary literature indexed under this exact term dates from the 1980s and 1990s and is descriptive, cell-culture or animal work.
• The term is a category, so findings about one factor — for example Steel factor in PMID 1381360 — do not transfer automatically to another.
• Several cited reports used transformed or leukemic cell lines, such as the WEHI-3B line characterised in PMID 3921392, which behave differently from primary marrow cells.
• Recombinant colony-stimulating factors exist as regulated prescription medicines in some jurisdictions; regulatory status is separate from the research literature described here.

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical question. Nothing here describes or endorses use of any substance in humans.

References

• Inhibition of hemopoietic growth factor-induced proliferation by adenosine diphosphate-ribosylation inhibitors (Blood, 1987)
• Tissue distribution of murine hemopoietic growth factor mRNA production (Journal of Cellular Physiology, 1989)
• Interaction of serum and colony-stimulating factor for survival of a factor-dependent hemopoietic progenitor cell line (Journal of Cellular Physiology, 1989)
• Hemopoietic growth factor receptor abnormalities in leukemia (Leukemia Research, 1998)
• The differential inhibition of hemopoietic growth factor activity by cytotoxins and interferon-gamma (Journal of Immunology, 1987)
• Characterization of hemopoietic growth factors from T cells and the myelomonocytic leukemia WEHI-3B (Experimental Hematology, 1985)
• Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells (Experimental Hematology, 1988)
• Bone marrow adherent cell hemopoietic growth factor production (Progress in Clinical and Biological Research, 1985)
• Hierarchical down-modulation of hemopoietic growth factor receptors (Cell, 1985)
• Hemopoietic growth factor gene transfer (Transplantation Proceedings, 1989)
• Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage (Cell, 1987)
• Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells (Journal of Biological Chemistry, 1992)