Disease relevance of Myelopoiesis

• These results indicate that recombinant human GM-CSF is effective in stimulating myelopoiesis in patients with severe aplastic anemia and may benefit some patients in whom the disorder is refractory to standard forms of therapy [1].
• Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a key cytokine in myelopoiesis and aberrant expression is associated with chronic inflammatory disease and myeloid leukemias [2].
• We bred homozygous, double-mutant me(v)/me(v) x RAG 1 -/- mice and found that, in fact, inflamed paws, and splenomegaly with elevated myelopoiesis [3].
• Mice with severe combined immunodeficiency syndrome (SCID) exhibit an impairment in both T and B cell maturation, whereas myelopoiesis remains unaffected [4].
• Thus, the present study suggests that p75/AIRM1 and CD33 may play a regulatory role in normal myelopoiesis and may be viewed as suitable target molecules to counteract the proliferation/survival of chronic myeloid leukemias [5].

High impact information on Myelopoiesis

• The AP-1 transcription factor JunB is a transcriptional regulator of myelopoiesis [6].
• These data provide evidence of NF1 may function as a tumor-suppressor allele in malignant myeloid diseases in children with NF-1 and that neurofibromin is a regulator of ras in early myelopoiesis [7].
• Limitation of excessive myelopoiesis by the intrinsic modulation of macrophage-derived prostaglandin E [8].
• Therefore, Bcl-XL functions as a key cytokine regulated anti-apoptotic protein in myelopoiesis and contributes to leukemia cell survival [9].
• Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha [10].

Chemical compound and disease context of Myelopoiesis

• These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis [11].
• Hemorrhagic shock inhibits lipopolysaccharide-induced myelopoiesis in both germ-free and conventional rats [12].
• Prostaglandin E2 receptor antagonist (SC-19220) treatment restores the balance to bone marrow myelopoiesis after burn sepsis [13].
• Influence of high versus low intestinal concentration of gram-negative bacteria and endotoxin on the susceptibility of murine myelopoiesis in bone marrow and spleen to cytostatic treatment with Ara-C [14].
• In this case of steroid-responsive LGL-associated neutropenia, laboratory studies suggested direct suppression of myelopoiesis by steroid-responsive LGL [15].

Biological context of Myelopoiesis

• By contrast, hematopoietic cells arising in the third week yolk sac, as well as their progeny at later stages, were restricted to myelopoiesis and therefore are unlikely to contribute to definitive hematopoiesis in man [16].
• The cytokine Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) regulates proliferation, differentiation, and apoptosis during myelopoiesis and erythropoiesis [17].
• Mice lacking the chemokine stromal cell-derived factor/pre-B cell growth stimulating factor or its primary physiological receptor CXCR4 revealed defects in B lymphopoiesis and bone marrow myelopoiesis during embryogenesis [18].
• The observations suggest that cyclin A1 overexpression results in abnormal myelopoiesis and is necessary, but not sufficient in the cooperative events inducing the transformed phenotype [19].
• Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human long-term marrow cultures [20].

Anatomical context of Myelopoiesis

• Increases beyond a critical concentration of colony stimulating factor within the local milieu of the mononuclear phagocyte induces the coincident elaboration of prostaglandin E, a self-regulated response which serves to limit the unopposed humoral stimulation of myelopoiesis [8].
• Previous attempts at identifying the constitutive source(s) of granulocyte colony-stimulating factor (G-CSF) in human bone marrow have been unsuccessful despite the fact that normal bone marrow supports abundant myelopoiesis in vivo [21].
• Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein hormone that specifically stimulates both production and functional activation of neutrophils, while interferon-alpha (IFN-alpha) is known to suppress myelopoiesis, including neutrophil production in vivo and in vitro [22].
• Because exogenous CSF stimulates myelopoiesis, it is likely that it too can react either directly or through microenvironmental cells to stimulate primitive myeloid cells to divide [23].
• We have shown previously that basic fibroblast growth factor (bFGF) is a mitogen for human bone marrow (BM) stromal cells and that bFGF stimulates myelopoiesis in primary BM cultures [24].

Associations of Myelopoiesis with chemical compounds

• We show here that in human long-term bone marrow culture antibodies recognizing a CD44 NH2-terminal epitope (mab 25-32) or a CD44v6 epitope (mab VFF18) inhibit myelopoiesis [25].
• Purified human lactoferrin was assessed for its influence in vivo in untreated mice and in mice undergoing rebound myelopoiesis after sublethal dosages of Cytoxan [26].
• In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2 [27].
• Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor [28].
• Taken together, the data indicate that vitamin A present in human plasma has inhibitory as well as stimulatory effects on myelopoiesis [29].

Gene context of Myelopoiesis

• Collectively, these findings indicate a novel role of IL-13 in early myelopoiesis, partially overlapping but also different from that of IL-4 [30].
• Comparative effects in vivo of recombinant murine interleukin 3, natural murine colony-stimulating factor-1, and recombinant murine granulocyte-macrophage colony-stimulating factor on myelopoiesis in mice [31].
• Transgenic expression of PML/RARalpha impairs myelopoiesis [32].
• These data suggest that abnormal myelopoiesis due to PML/RARalpha expression is an early event in oncogenic transformation [32].
• We propose that Meis1a and Hoxa9 are part of a molecular switch that regulates progenitor abundance by suppressing differentiation and maintaining self-renewal in response to different subsets of cytokines during myelopoiesis [33].

Analytical, diagnostic and therapeutic context of Myelopoiesis

• G-CSF accelerates myelopoiesis following the infusion of 4-hydroperoxycyclophosphamide-purged autologous marrow and shortens hospitalization [34].
• In situ hybridization and immunohistochemical studies demonstrated that BNBD-4 synthesis is completed early in myelopoiesis [35].
• Bone marrow changes in adjuvant-induced and collagen-induced arthritis. Interleukin-1 and interleukin-6 activity and abnormal myelopoiesis [36].
• Because intact c-Myb and Ets-2 proteins, both endogenously expressed in myeloid cells, act synergistically to transactivate the CD13/APN promoter, this gene may represent a physiological target for dissection of the roles of these transcription factors in normal and malignant myelopoiesis [37].
• MATERIALS AND METHODS: Mobilization by intravenous injection of anti-CD44, anti-VLA4, or G-CSF was controlled in spleen and bone marrow with regard to frequencies of multipotential colony-forming unit (C-CFU), marrow repopulating ability, long-term reconstitution, recovery of myelopoiesis, and regain of immunocompetence [38].

References