scholarly journals Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors

Leukemia ◽  
2003 ◽  
Vol 17 (9) ◽  
pp. 1713-1721 ◽  
Author(s):  
A L Dewar ◽  
R M Domaschenz ◽  
K V Doherty ◽  
T P Hughes ◽  
A B Lyons
1993 ◽  
Vol 3 (3) ◽  
pp. 197-210 ◽  
Author(s):  
Heike Pohla ◽  
Medi Adibzadeh ◽  
Hans-Jörg Bühring ◽  
Petra Siegels-Hübenthal ◽  
Thomas Deikeler ◽  
...  

In order to study extrathymic differentiationin vitro, CD7+CD3-lymphocytes were sorted from normal human bone marrow and cultured under conditions of limiting dilution together with irradiated pooled allogeneic peripheral blood mononuclear cells (PBMC) and phytohemagglutinin (PHA) in the presence of 1000 U/ml of interleukin-2 (IL-2). One clone was obtained that failed to react with monoclonal antibody (mAb) TCRδ1 (TCRγ/δ-specific) or WT31 (TCR2,α/β-specific). From day 35 through day 74 in culture, the surface phenotype of this clone evolved into CD3+, CD4+, CD8-, TCR2+, TCR1-, and was further characterized as CD2+, CD45RO+, CD16-, and CD56-. The presence of mRNA for TCRαandγbut not ,andγchains was confirmed by Northern blotting. Accessory cell-dependent autocrine proliferative responses to PHA (most likely driven by IL-2) were initially absent, but became measurable at the same time as the TCR was acquired. However, in the absence of PHA, the clone failed to respond to a panel of homozygous B-cell lines representing the majority of MHC class II alleles. Autoreactivity was also not demonstrable. Cytotoxicity was limited to MHC unrestricted “natural killer (NK)-like” lysis of K562 target cells, with no autocytotoxicity detected. Tle NK-like lysis diminished over time in parallel with the acquisition of surface TCR. The cloned cells were not suppressive for mature lymphocyte proliferation. After stimulation, the cells secreted tumor necrosis factorαand granulocyte/macrophage colony-stimulating factor (GM-CSF) detected by immunoassays, and T-cell growth factors, most likely IL-2, as detected by bioassays. Polymerase chain-reaction methods demonstrated the presence of mRNA for IL-2, IL-3, IL-4, IL-9, interferon-δ, and GM-CSF in these cells after stimulation with PHA and B-LCL.These results suggest that cells with the phenotype and some functional characteristics of mature T lymphocytes can evolve extrathymicallyin vitrofrom T-cell precursors sorted from normal human bone marrow.


Blood ◽  
1977 ◽  
Vol 49 (3) ◽  
pp. 415-424
Author(s):  
N Jacobsen

Normal human bone marrow contains cells capable of forming colonies of hemopoietic cells in fibrin clots in diffusion chambers implanted intraperitoneally (i.p.) into irradiated mice. The present paper describes the proliferation of such colony-forming units (CFUD) in cultures in vivo. Cells harvested from diffusion chambers after 1–14 days of culture in 450-R irradiated mice contained CFUD, which formed neutrophilic, eosinophilic, or megakaryocytic colonies when tested by secondary culture in fibrin clot chambers. When bone marrow was precultured in irradiated mice at a concentration of 10(6) cells per chamber, an initial fall in the number of neutrophilic CFUD was observed. This decrease was followed by an increase to a maximum at day 2, and then a secondary decrease. The number of neutrophilic CFUD recovered after 2 days of preculture in irradiated mice varied between 60% and 250% of the number present before preculture. Preculture in nonirradiated mice resulted in a significantly lower recovery of neutrophilic CFUD. In vitro treatment of bone marrow cells with hydroxyurea (OHU) after 2 days of preculture in irradiated mice resulted in a 68% +/- 5% reduction in the number of neutrophilic CFUD. In contrast, OHU had no similar effect on precultures from nonirradiated mice. Both the recovery and sensitivity to OHU of eosinophilic CFUD were independent of host irradiation. Similarly, no effect of host irradiation on the recovery or the 3H-thymidine (3HTdR) labeling index of morphologically recognizable granulocytic cells was observed at day 2. The data suggest an effect of humoral host factor(s) on the proliferation of early precursor cells, which are or become committed to differentiate into the neutrophilic pathway in diffusion chambers.


1983 ◽  
Vol 5 (1) ◽  
pp. 51
Author(s):  
H.C. Freake ◽  
D.M. McCarthy ◽  
J.F. San Miguel ◽  
P.M. Green ◽  
H. Zola ◽  
...  

1993 ◽  
Vol 4 (6) ◽  
pp. 309-313 ◽  
Author(s):  
V. S. Gallicchio ◽  
N. K. Hughes

Zidovudine, the antiviral drug used in the treatment of acquired immunodeficiency syndrome (AIDS), causes toxicity to the haematopoietic system. Although use of the haematopoietic growth factors, GM-CSF and erythropoietin have been investigated in clinical trials to modulate antiviral toxicity, there is scant data which supports their ability to ameliorate zidovudine induced toxicity on haematopoietic progenitor cells when combined in vitro. We describe here the results of studies designed to evaluate the capacity of additional haematopoietic factors such as granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) to modulate zidovudine-induced toxicity on G-CSF and M-CSF dependent-colony formation in the presence or absence of zidovudine in vitro. These factors were also studied combined with erythropoietin in culture for the early erythroid progenitor BFU-E using adherent, T-cell, depleted normal human bone marrow cells in the presence or absence of zidovudine. In the presence of zidovudine at the concentration producing 50% inhibition of G- and M-CSF dependent colony formation, (5 × 10−5M), dose-escalation of either G-CSF or M-CSF failed to ameliorate zidovudine toxicity. However, in the presence of zidovudine at the concentration that produces 50% inhibition of BFU-E (5 × 10−9M), and optimal erythropoietin (1 unit ml−1), G-CSF ameliorated zidovudine inhibition of BFU-E, which was not observed with M-CSF. In the presence of erythropoietin, G-CSF increased significantly normal BFU-E. These studies indicate that G-CSF may be useful in ameliorating zidovudine-induced anaemia and suggest G-CSF may act as a synergistic factor to enhance erythropoietin to support the growth of erythroid progenitors in conditions where erythropoitin is ineffective.


2005 ◽  
Vol 126 (1-2) ◽  
pp. 91-100 ◽  
Author(s):  
Luisa Bertolini ◽  
Maria Luisa Aebischer ◽  
Franco Ameglio ◽  
Antonio Angeloni ◽  
Isabella Delaroche ◽  
...  

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