Myeloid progenitors

CML is a hematologic cancer that results from an abnormal proliferation of an early myeloid progenitor cell.1 The clinical course of CML has three phases chronic phase, accelerated... 

Broxmeyer HE, Sherry B, Lu L, et al. Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells. Blood 1990 76(6) 1110—1116. 

Broxmeyer HE, Sherry B, Cooper S, et al. Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression. J Immunol 1993 150(8 Pt... 

Broxmeyer HE, Cooper S, Cacalano G, Hague NL, Bailish E, Moore MW. Involvement of Interleukin (IL) 8 receptor in negative regulation of myeloid progenitor cells in vivo evidence from mice lacking the murine IL-8 receptor homologue. 

Broxmeyer HE, Cooper S, Kohli L, et al. Transgenic expression of stromal cell-derived factor-l/CXC chemokine ligand 12 enhances myeloid progenitor cell sur-vival/antiapoptosis in vitro in response to growth factor withdrawal and enhances myelopoiesis in vivo. J Immunol 2003 170(1) 421 429. 

Broxmeyer HE, Kohli L, Kim CH, et al. Stromal cell-derived factor-l/CXCL12 directly enhances survival/antiapoptosis of myeloid progenitor cells through CXCR4 and G(alpha)i proteins and enhances engraftment of competitive, repopulating stem cells. J Leukoc Biol 2003 73(5) 630-638. 

Lymphoid and myeloid progenitors appear in fetal liver — 7-825 1Q21,67,73,81... 

Lymphoid myeloid progenitor cells first appear in fetal liver... 

The first site of myelopoiesis75 in the mouse embryo is the fetal liver, where the common myeloid progenitor, the megakaryocyte-erythrocyte-restricted progenitors and granulocyte-monocyte restricted progenitors are present. Myelopoiesis occurs in the fetal liver in the same manner as in adult bone marrow.81 However, the proliferation capacity, colony forming activity and differentiation capacity is different between the fetal liver and adult bone marrow.81... 

Palis, J., et al. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse, Development, 126, 5073, 1999. 

Mixed myeloid progenitor cell Lymphoid progenitor cell... 

Figure 3. Scatterplot of dependency of CD34+33+ myeloid progenitor cell counts (Y axis, cells per 10 3) from CD34+33- cell number (axis X, cells per 10 3).

Kuo, Y., Landrette, S., Heilman, S., Perrat, P., Garrett, L., Liu, P., Beau, M.L., Kogan, S. and Castilla, L. (2006) Cbfp SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia. Cancer CellQ, 57-68. 

Erickson-Miller, C.L., May, R.D., Tomaszewski, J., Osborn, B., Murphy, M.J., Page, J.G. and Parchment, R.E. (1997) Differential toxicity of camptothecin, otpotecan and 9-amino-camptothecin to human canine and murine myeloid progenitors (CFU-GM) in vitro. Cancer Chemotherapy and Pharmacology, 39, 467-474. 

An example is a chemokine called myeloid progenitor inhibitor factor-1 (MPIF-1), developed by Human Genome Sciences (HGS) for the treatment of patients with cancer to reduce the toxicity of chemotherapy. It was the hrst genomics-derived therapeutic product to enter clinical trials [37]. 

Although IFN-a and IFN-P have approximately 30% amino acid homology, antisera to IFN-a and IFN-P do not cross-react. Interestingly both compete for the same cellular receptor. In vitro studies demonstrate greater antiproliferative effects of IFN on different nonhemato-poietic cell lines and fibroblasts compared to IFN-a2 [59,60]. However, on lymphoid-derived (Daudi) cell lines or other myeloid progenitor cells, IFN-a displayed greater antiproliferative effects [59]. TTie antiproliferative effects of IFN-P have been shown to be in part due to induction of apoptosis... 

Hydrogen peroxide transformed mouse myeloid progenitor cells (FDC-Pl) from interleukin-3 dependence to factor independence, but only at cytotoxic concentrations (> 12/5 pmol/L). Such a transformation was not induced by non-specific insults to the cells, such as sodium fluoride or heat shock treatment. The transformed cells produced tumours when injected into pre-irradiated mice (Crawford Greenberger, 1991). Hydrogen peroxide (10 pmol/L) induced overexpression of the proto-oncogene c-jun in hamster tracheal epithelial (HTE) cells c-jun overexpression led to proliferation and increased growth rate, as well as increased anchorage-independence of HTE cells (Timblin et al., 1995). 

Crawford, D.R. Greenberger, J. S. (1991) Active oxygen transforms murine myeloid progenitor cells in vitro. Int. J. Cancer, 49, 744-749... 

Hydroquinone has been extensively studied. Carbonnelle et al. (1995) have investigated the effect of hydroquinone on IL-1 release from human monocytes, in an effort to show that reduced interleukin release my inhibit cytokine release by monocytes, thereby adversely affecting the regulation of hematopoiesis. Support for this mechanism comes from the work of Miller et al. (1994) who showed that hydroquinone decreased the enzyme responsible for the conversion of interleukin precursors in murine bone marrow macrophages. In addition, hydroquinone has been shown to alter differentiation of myeloid progenitor cells which may be important to benzene leukemogenesis (Irons and Stillman 1993 Irons et al. 1992). 

Rajarathnam, K., Li, Y., Rohrer, T., and Gentz, R. (2001). Solution structure and dynamics of myeloid progenitor inhibitory factor-1 (MPlF-1), a novel monomeric CC chemokine. / Biol. Chem. 276, 4909-4916. 

A number of cytokines (see p. 280) stimulate the growth, differentiation and functional activity of myeloid progenitor cells. As the name implies the function of these polypeptides was defined by in-vitro colony assays of bone marrow progenitors. They have effects on all myeloid cells including the multipotential stem cells (but probably not the more immature pluripotentiai cells), intermediate progenitors and circulating mature cells. Those in clinical use are described below. 

Since thiamphenicol, which causes very few cases of aplastic anemia, differs from chloramphenicol by substitution of the para-nitro group by a methylsulfonyl group, interest has been focused on the para-nitro group and metabolites of that part of the molecule, nitrosochlor-amphenicol and chloramphenicol hydroxylamine. In human bone marrow, nitrosochloramphenicol inhibited DNA synthesis at 10% of the concentration of chloramphenicol required for the same effect, and prohferation of myeloid progenitors was irreversibly inhibited. The covalent binding of nitrosochloramphenicol to marrow cells was 15 times greater than that of chloramphenicol... 

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