Peripheral blood cells of 21 patients with different forms of acute leukemia were cultured in diffusion chambers (5 x 10(5) cells/chamber) implanted intraperitoneally in 650 R preirradiated host mice over a period of up to 21 days. In patients with acute myeloid leukemia (AML), acute erythroleukemia (AEL), or acute myelomonocytic leukemia (AMMoL), the total number of cells which developed durin...

Corticosteroids cause an enhanced return of granulopoiesis as measured by in vitro growth of granulocytic progenitor cells (CFU-C) in mice treated with cyclophosphamide. After methylprednisolone and cyclophosphamide, a greater than threefold increase in marrow CFU-C was measured on day 4 compared to mice given cyclophosphamide alone (29,700+/-200 vs. 8,400+/-700/humerus). The accelerated return...

The purpose of this study was to invostigate mechanisms of action and in vivo relationships of serum factors that regulate granulopoiesis in vitro. Granulopoiosis involves interactions between stimulating and proliferating cells, and in order to determine mechanisms of action it is necessary to assess whether an activity acts on the stimulating or on the proliferating cell. Liquid cultures of m...

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein believed to play an important role in regulating granulopoiesis both at steady state and during an "emergency" situation. Generation of G-CSF and G-CSF receptor-deficient mice by gene targeting has demonstrated unequivocally the importance of G-CSF in the regulation of baseline granulopoiesis. This study attempted to define the phy...

The transcription factor CCAAT enhancer binding protein α (C/EBPα) is a master regulator in granulopoiesis and is frequently disrupted in acute myeloid leukemia (AML). We have previously shown that C/EBPα exerts its effects by regulating microRNAs (miRs) such as miR-223 and miR-34a. Here, we confirm miR-30c as a novel important target of C/EBPα during granulopoiesis. Thus, wild-type C/EBPα-p42 ...

Specific alterations in the microvascular and connective tissue compartments of the hemopoietic microenvironment have been examined during erythropoietic regeneration and suppression in the murine spleen and bone marrow using in vivo microscopic and histochemical methods. The results have confirmed the concept of specific hemopoietic microenvironments and have demonstrated specific alterations ...

The transcription factor C/EBP alpha (CCAAT/enhancer binding protein alpha) is critical for granulopoiesis. Gene disruption in mice blocks early granulocyte differentiation and disruption of C/EBP alpha function has been implicated in human acute myeloid leukemia (AML), but no systematic structure-function analysis has been undertaken to identify the mechanisms involved in C/EBP alpha-mediated ...

apoptosis. As the authors note, the phenotypic features of C/EBP -deficient granulopoiesis resemble those of a myelodysplastic syndrome. Because C/EBP mutations and/or dysfunction are known to be involved in the pathogenesis of acute myeloid leukemia (AML), it is possible that inactivation of other C/EBP proteins such as C/EBP play a role in myeloid disorders (MDSs) as well. For example, C/EBP ...

The transcription factor LEF-1 (lymphoid enhancer-binding factor 1), which plays a definitive role in granulocyte colony-stimulating factor receptor (G-CSFR)-triggered granulopoiesis, is downregulated in granulocytic progenitors of severe congenital neutropenia (CN) patients. However, the exact mechanism of LEF-1 downregulation is unclear. CN patients are responsive to therapeutically high dose...

The in vivo roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF were studied in factor-deficient gene-targeted knockout mice infected with the facultative intracellular bacterium Listeria monocytogenes. Previous results showed that G-CSF-/- mice had an underlying selective deficiency in granulopoiesis, but GM-CSF-/- mice had little disturbance in resting h...