Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship of the leukemogenic and natural killer (NK)-suppressive effects of fractionated doses of gamma-radiation in mice was studied. A/J mice were relatively resistant; CBA/J, BALB/c, and C57BL/6 were susceptible to both the NK-suppressive and leukemogenic effects, and young (1 mo old) C57BL/6 mice were more susceptible than were 2- and 3-month-old C57BL/6 mice to both effects. Age-dependent susceptibility to radiation-induced leukemogenesis also was observed in C57BL/6 (bg/bg) (beige) mice. No differences in incidence and latent period of lymphoma development were found between C57BL/6 (+/+) and beige mice. Bone marrow cells (BMC) from normal C57BL/6 donors reconstituted the NK reactivity of irradiated C57BL/6 (+/+) or beige recipients and inhibited leukemogenesis. Although BMC of beige donors did not reconstitute the NK reactivity of irradiated C57BL/6 (+/+) or beige recipients, these cells were as efficient for antileukemic protection as were BMC from C57BL/6 (+/+) mice. The bone marrow of irradiated mice contained preleukemia cells that produced leukemias when transplanted iv into recipients preirradiated with 400 R. Inoculation (iv) of spleen cells (SpC) from syngeneic nude mice plus preleukemia bone marrow cells (PBMC) were able to inhibit leukemia formation in the 400 R-irradiated recipients. SpC from beige mice, normal C57BL/6 (+/+) mice, or C57BL/6 (+/+) mice treated with anti-asialo GM1 serum had no influence on the development of leukemia after their transplantation with PBMC.
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PMID:Evaluation of role of natural killer cells in radiation-induced leukemogenesis in mice. 637 39

Patients with myelodysplasia (MDS) show an impaired reactive oxygen species (ROS) production in response to fMLP stimulation of GM-CSF-primed neutrophils. In this study, we investigated the involvement of lipid rafts in this process and showed that treatment of neutrophils with the lipid raft-disrupting agent methyl-beta-cyclodextrin abrogates fMLP-induced ROS production and activation of ERK1/2 and protein kinase B/Akt, two signal transduction pathways involved in ROS production in unprimed and GM-CSF-primed neutrophils. We subsequently showed that there was a decreased presence of Lyn, gp91(phox), and p22(phox) in lipid raft fractions from neutrophils of MDS. Furthermore, the plasma membrane expression of the lipid raft marker GM1, which increases upon stimulation of GM-CSF-primed cells with fMLP, was reduced significantly in MDS patients. By electron microscopy, we showed that the fMLP-induced increase in GM1 expression in GM-CSF-primed cells was a result of de novo synthesis, which was less efficient in MDS neutrophils. Taken together, these data indicate an involvement of lipid rafts in activation of signal transduction pathways leading to ROS production and show that in MDS neutrophils, an impaired lipid raft formation in GM-CSF-primed cells results in an impaired ROS production.
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PMID:The reduced GM-CSF priming of ROS production in granulocytes from patients with myelodysplasia is associated with an impaired lipid raft formation. 1707 51