Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After orthotopic transplantation of rat livers from Lewis (LEW) donors into Wistar Furth (WF) recipients, a rejection response occurs 2 weeks after transplantation, followed by indefinite survival of the transplant. Spleen cells from WF rats bearing long-term LEW liver grafts responded in MLR and CML assays like spleen cells from normal WF rats after in vitro stimulation with mitomycin C-treated LEW spleen cells, but did not generate CTL after stimulation with paraformaldehyde-treated LEW spleen cells. Transient damage to the long-term grafted livers was induced by inoculation of recipients with homogenized normal LEW liver. CD8+ CTL were detected in the spleen at the time of this liver damage. These findings indicate that CTL precursors are present in WF rats bearing LEW liver transplants. These CTL precursors are capable of differentiating into effector CTL in vitro and in vivo in response to donor antigen. However, once generated, effector CTL in WF rats are eliminated or become unresponsive to the transplanted LEW liver. Homogenized LEW liver from grafted donors did not induce transient liver damage when inoculated into recipient WF rats bearing LEW liver transplants. The demonstration of large amounts of antibody bound to either parenchymal or nonparenchymal cells in the donor graft suggests that reduction (or loss) of antigenicity could also be responsible for the inability of LEW liver to elicit an immune response in WF-recipient rats. Thus, elimination or inactivation of effector CTL and altered antigenicity could both be responsible for maintaining tolerance after allogeneic liver transplantation.
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PMID:Long-term survival of orthotopic Lewis liver grafts in Wistar Furth rats. Elimination or inactivation of effector CTL and altered antigenicity as possible reasons for tolerance. 810 77

We studied whether it is possible to obtain sufficient mRNA from old paraffin-embedded samples of spleen and bone marrow for reverse transcription and polymerase chain reaction analysis. Spleen tissue from 6 subjects with chronic myelogenous leukemia was studied for rearrangement of BCR and ABL genes. Analysis was successful in 4 cases. These data indicate the feasibility of retrospective analysis of tissue samples of special interest by molecular techniques.
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PMID:Analysis of BCR/ABL abnormalities in mRNA from 20-year-old paraffin-embedded tissue for BCR/ABL rearrangement by polymerase chain reaction. 823 76

Spleen size ranks among the most important risk factors in chronic myeloid leukemia (CML), but the pathogenic mechanisms of splenic hematopoiesis in CML remain poorly defined. Here, we studied the biology of Bcr-Abl positive leukemia-initiating cells in the spleen, using an inducible transgenic mouse model of CML. Disease kinetics showed greater increases of immature leukemic cells in spleen vs bone marrow (BM). To assess how Bcr-Abl alters the behavior of spleen-derived CML cells, we transplanted these cells either before ('pre-uninduced') or 44 days after ('pre-induced') expression of the oncogene. Mice transplanted with pre-induced spleen cells showed significantly increased neutrophilia and splenomegaly compared with mice receiving pre-uninduced spleen cells, suggesting that Bcr-Abl expression in the donors had increased splenic tumor burden. However, pre-induction also altered the biology of these cells, as shown by a striking increase in erythropoietic potential. These results differ from those of BM-derived CML stem cells where pre-induction of Bcr-Abl had previously been shown to decrease disease transplantability. Moreover, splenic cells were less sensitive to imatinib than BM cells. In conclusion, Bcr-Abl alters the biology of splenic leukemic stem cells by a cell-autonomous mechanism, but the disease phenotype is also influenced by the microenvironment of these cells.
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PMID:Leukemic spleen cells are more potent than bone marrow-derived cells in a transgenic mouse model of CML. 2219 68


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