Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied a variant CD5- B cell chronic lymphocytic leukemia (CLL) cell population that produces pathologic IgM kappa rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell CLL, these leukemia cells rapidly undergo cell death hours after being placed in tissue culture. We find that addition of Ag (aggregated human IgG) enhances significantly the survival of these cells in vitro. Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the leukemia cells' surface IgM receptors with immobilized murine mAb specific for human Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack of bcl-2 expression may render these leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B cell leukemias and lymphomas.
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PMID:Autoantigen inhibits apoptosis of a human B cell leukemia that produces pathogenic rheumatoid factor. 750 24

Low-grade follicular non-Hodgkin's lymphomas are characterized by the presence of a t(14;18) chromosomal translocation that results in deregulation of the B-cell lymphoma (Bcl-2) gene. Studies in cell lines and transgenic animal models have suggested that this results in the suppression of apoptotic cell death in germinal centers. B lymphocytes from normal germinal centers and lymph nodes infiltrated by follicular lymphoma were isolated by immunomagnetic depletion of cells bearing CD4, CD8, or slgD for study in vitro. Follicular lymphoma cells expressing Bcl-2 protein were shown to resist apoptosis after isolation, and could be induced to proliferate in a culture system previously described for the growth of normal B lymphocytes. By the use of a mouse fibroblast monolayer transfected with the CDw32 Fc receptor to present CD40 monoclonal antibody in the presence of interleukin-4, prolonged culture was possible. Karyotypic analysis of cultured lymphoma cells showed the t(14;18) translocation, with clonal identity confirmed by polymerase chain reaction amplification of the breakpoints and direct sequence analysis. These findings support the hypothesis that resistance to apoptosis is an influence on the initiation of follicular lymphoma, and provide a novel means of studying in vitro the intercellular reactions that may be important in progression of the disease.
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PMID:Isolated follicular lymphoma cells are resistant to apoptosis and can be grown in vitro in the CD40/stromal cell system. 769 Dec 40