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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine secreted by a human hybrid B cell line (STS 25) obtained by fusion of the B lymphoblastoid cell line WI-L2-729-HF2 with neoplastic B cells from a patient with B cell non-Hodgkin's lymphoma (B-NHL) was characterized as IL-1 alpha. STS 25 cells express the idiotypic (Id+) immunoglobulin (Ig) specific for the neoplastic B cells of the B-NHL patient. STS 25 cells are weakly positive for surface mu delta kappa and in addition express the surface markers CD19, CD20, CD23, HLA class I and II, and the 4F2 activation antigen. STS 25 cells are also Epstein-Barr nuclear antigen positive but do not secrete viral particles. Serum-free culture supernatant from STS 25 cells (STS 25 SUP) does not show activity in assays for interleukin-2 (IL-2), -4 (IL-4), -6 (IL-6), interferon or tumor necrosis factor, but is active in the thymocyte costimulation assay and the D10.G4.1 T helper clone proliferation assay for interleukin-1 (IL-1). The IL-1 character of the STS 25 SUP activity was confirmed in inhibition studies with three different poly- or monoclonal anti-IL-1 antibodies (31, 88, and 94% inhibition in thymocyte costimulation assay, respectively). Furthermore, complete blocking of D10.G4.1 cell proliferation mediated by STS 25 SUP was observed by including anti-IL-1 alpha specific antibody in the assay, whereas anti-IL-1 beta antibody had no effect. These results indicate that this STS 25 SUP activity can be attributed to the presence of IL-1 alpha in the supernatant. Northern blot analysis of total STS 25 cellular RNA using IL-1 alpha or IL-1 beta specific probes revealed the constitutive expression of IL-1 alpha messenger RNA by STS 25 cells. In contrast, no IL-1 beta message was detectable, not even after treatment of the cells with phorbol ester or cycloheximide, which resulted in approximately 5-fold enhancement of IL-1 alpha mRNA expression. Binding studies with radiolabeled recombinant (r) IL-1 alpha indicated the presence of high numbers of IL-1 receptors on STS 25 cells (1,170 per cell, Kd = 392 pM). Although both IL-1 alpha and IL-1 beta bound to these IL-1 receptors, no indication was found for IL-1 mediated regulation of STS 25 cell growth.(ABSTRACT TRUNCATED AT 400 WORDS)
Leukemia 1989 Aug
PMID:Functional and molecular characterization of B cell line derived interleukin-1 alpha. 278 53

In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
Leukemia 1989 Aug
PMID:Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells. 217 41

Treatment of murine B cells with bacterial lipopolysaccharide (LPS) in the presence or absence of different lymphokines results in cell populations that differentially express particular immunoglobulin heavy chain constant region (CH) genes. This class switch involves recombination between switch regions located upstream of the germ-line CH genes. We have treated Abelson murine leukemia virus-transformed pre-B cells and normal splenic B cells with LPS or LPS plus the lymphokine IL-4 and examined the effect on the germ-line gamma 2b locus and gamma 2b class switching. In both cell types, LPS induces transcription specifically through the germ-line gamma 2b locus before gamma 2b class switching. Furthermore, IL-4 inhibits LPS induction of germ-line gamma 2b transcripts in spleen cells and correspondingly abrogates switching to this CH gene. Thus treatment with mitogens and lymphokines can alter transcription of germ-line CH genes in B lineage cells and thereby directly regulate class switching in the context of a recombinase accessibility mechanism.
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PMID:Mitogen- and IL-4-regulated expression of germ-line Ig gamma 2b transcripts: evidence for directed heavy chain class switching. 283 63

T cell-replacing factor (TRF) is known to play a critical role in the regulation of B cell growth and differentiation. In this study, the role of TRF in the expression of mRNA for both IgM and IgG1 class was investigated. The TRF was purified from cellfree supernatants from a T cell hybridoma, B151K12. RNA was isolated from chronic B cell leukemia (BCL1) cells, DNP-KLH-primed B cells, or normal B cells cultured with or without LPS, and LPS plus TRF or LPS plus BSF-1. The steady state level of isotype-specific mRNA was assessed by Northern blot analysis with a mu-specific or a gamma 1-specific probe. It was demonstrated that BCL1 and purified B cells cocultured with TRF expresses increased levels (twofold and fourfold, respectively) of secreted forms of mu mRNA. Purified B cells from DNP-KLH-primed mice also expressed increased levels (twofold to fourfold) of mu as well as gamma 1 mRNA for secreted form by stimulation with TRF. Total expression of mu mRNA, however, was approximately threefold higher than that of gamma 1 mRNA. The stimulation of normal B cells with LPS plus TRF induced an increase in the levels of mu mRNA and gamma 1 mRNA expression, fourfold and threefold, respectively. However, the levels of gamma 1 mRNA expression was one-third of that induced in B cells stimulated with LPS plus BSF-1. These results indicate that TRF preferentially induces increased levels of secreted type of mu mRNA and induces less gamma 1 mRNA than BSF-1. The differential role of TRF from BSF-1 in the expression of Ig mRNA will be discussed.
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PMID:Role of T cell-replacing factor (TRF) in the murine B cell differentiation: induction of increased levels of expression of secreted type IgM mRNA. 310 2

Tumor cells from 5 human B cell non-Hodgkin's lymphoma (B-NHL) patients were investigated for proliferative activity and idiotypic (Id+) immunoglobulin (Ig) secretion in serum-free medium without deliberate addition of B cell growth or differentiation factors (BCDF). These data were compared with cell surface marker expression, notably of activation antigens such as 4F2 and interleukin-2 (IL-2) receptor. Cells from all patients became 4F2 positive at the end of the 6-day culture period. Freshly drawn cells from 3 out of 5 patients expressed the IL-2 receptor (CD25; Tac antigen) or acquired this marker during culture in vitro and secreted relatively high levels of Id+ Ig in vitro. This correlated with elevated serum Id levels (greater than or equal to 0.5 micrograms/ml in vitro versus greater than or equal to 20 micrograms/ml in vivo). In the 2 CD25 (Tac)- B-NHL patients serum Id levels were below the detection limit and the amount of Id+ Ig secreted in vitro did not surpass 50 ng/ml. Only the B-NHL cells from a single patient were initially CD25 (Tac) positive and only these cells proliferated in serum-free culture. To test whether IL-2 receptor expression in the 3 CD25 (Tac)+ patients was functional, recombinant IL-2 (rIL-2) either alone or in conjunction with BCDF and recombinant IL-4 (rIL-4) was added to the cultures. In 2 out of 3 CD25 (Tac)+ patients rIL-2 was capable of enhancing proliferation or Ig secretion. In addition rIL-2 was found to enhance BCDF-mediated but not rIL-4 mediated responses. The third CD25 (Tac)+ B-NHL population was resistant to any of these lymphokines. Thus, this serum-free culture system may accurately reflect patient serum Id levels. IL-2 appears to regulate not only the in vitro but also the in vivo Ig secretion by neoplastic B cells.
Leukemia 1988 Apr
PMID:Idiotypic immunoglobulin secretion by human B cell non-Hodgkin's lymphomas is related to the expression of the interleukin-2 receptor. 312 22

Prevention of high frequency spontaneous T cell lymphoma development in AKR mice by mAb 18-5 treatment was shown to involve inhibition of the recombinant Class I MCF virus formation and elimination of the early occurring potential lymphoma cells (PLCs). A low B cell lymphoma incidence (16% at a mean latency of 540 days) and a low level of PLCs (yielding 12% B cell lymphoma development following lymphoid cell transfer) was observed in mAb 18-5 treated mice (in contrast to a high PLC level in thymectomized AKR mice that could be experimentally triggered to progress to overt CD5+ B cell lymphomas). Administration of anti CD8 mAb or IL-4 to 12-month-old mAb 18-5 pre-treated mice only slightly increased B cell lymphoma incidence (up to 30-40%). Exposure to split-dose irradiation resulted in 26% B cell lymphomas at a 250 day mean latency. The phenotypes of the B lymphomas developing in mAb 18-5 treated mice were: B220+ (14.8+, 6B2+), 6C3+, Mac2+, CD5-. Most lymphomas expressed l-a and surface IgM, pointing to their mature B cell characteristics. Moreover, in some of the lymphomas, high levels of IgM production and secretion were determined. A comparison of the morphological characteristics (based on light and ultrastructure microscopy) of CD5+ and CD5- B cell lymphomas developing in AKR mice indicated marked differences. Analysis of the IgH locus of representative CD5- B lymphomas showed an identical pattern of IgH rearrangement in some tumors (similar to previous findings among CD5+ lymphomas). The virological analysis of the CD5- B cell lymphomas (similar to those observed in the CD5+ B cell lymphomas of AKR origin) showed that their development did not require formation of the pathogenic MCF recombinant viruses. The differences observed between the CD5+ and CD5- B cell lymphomas developing in AKR mice (following prevention of spontaneous T cell lymphomagenesis) may be due to their origin of different B cell precursors or from B cells at different levels of differentiation.
Leukemia 1995 Nov
PMID:The effects of passive anti-viral immunotherapy in AKR mice: II. Susceptibility to B cell lymphomagenesis. 747 87

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

PGM-2 is a variant of the transplantable PGM-1 leukemia of strain C3H/HeJ. Freshly explanted cells had lymphoid morphology with a CD5+ CD45R (B220)- IgM- phenotype. They were not viable in unstimulated cultures, but formed IgM+ lymphoid colonies in response to interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-7, and Steel factor, and macrophage colonies in response to IL-3. IL-3-stimulated colonies had no recloning potential, but colonies from IL-7 cultures gave rise to large numbers of secondary macrophage colonies in IL-3-stimulated cultures and secondary lymphoid colonies in IL-7-stimulated cultures. The latter ones could be serially transferred in vitro for several months, and formed typical PGM-2 tumors in vivo. IL-7-stimulated colonies could therefore be used to measure leukemic stem cells in vitro. Supramaximal IL-3 stimulation (2,500 U/mL) of suspension cultures was followed by an increase in overall cell numbers and a disappearance of leukemic stem cells, compatible with differentiation induction. This could not be counteracted by simultaneous stimulation with IL-7. However, lower IL-3 concentrations (500 U/mL) induced an expansion of the stem cell pool, possibly by facilitating density-dependent autostimulatory mechanisms involving endogenous production of IL-7. The system described is a simple in vitro model for differentiation therapy. It shows that leukemic stem cells can be induced by hematopoietic growth factors to undergo terminal differentiation, but the concentrations required for differentiation induction in stem cells are much higher than those required for other biologic effects. Submaximal stimulation may favor expansion rather than repression of the leukemic cell population.
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PMID:Self-renewal and differentiation of stem cells in a biopotential murine leukemia: an in vitro model for differentiation therapy. 751 9

Mast cells, mastocytoma cells and basophil leukaemia cells are well-established producers of leukotrienes when grown and stimulated appropriately. I report that the cells' ability to produce leukotrienes is dependent on the cells' proliferative status or their provision with growth factors. Proliferating MC/9 and subconfluent RBL2H3 cells respond maximally to stimulation by 1 microM ionomycin with the production of 56 and 32 pmol of cysteinyl-leukotrienes/10(6) cells respectively. In contrast, confluent RBL2H3 or growth-arrested MC/9 cells lose their ability to generate leukotrienes in response to ionomycin treatment. This rapid down-regulation of leukotriene synthesis is also observed when proliferating RBL2H3 cells are transferred to growth-factor-free medium, wherein cellular leukotriene-synthesis capacity has an apparent half-lifetime of 60 min. Transfer back into growth medium results in the regeneration of leukotriene synthesis capacity within 6 h. In growth-arrested MC/9 cells, leukotriene production ability can at least partially be restored by priming the cells with interleukin 3, but not with interleukin 4. In RBL2H3 cells, pretreatment with protein tyrosine kinase inhibitors such as genistein (5 min, 37 microM), herbimycin A (6 h, 3 microM) or tyrphostin 25 (16 h, 100 microM) completely inhibits leukotriene generation, whereas okadaic acid (15 min, 0.5 microM) has no effect. Under these conditions, both genistein and herbimycin A strongly impair ionomycin-induced protein tyrosine phosphorylation. Our study indicates that leukotriene generation in these tumour cells is tightly regulated by their proliferation status and supply with growth factors, and cell stimulation towards leukotriene synthesis appears to involve protein tyrosine kinase activity.
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PMID:Cell proliferation status, cytokine action and protein tyrosine phosphorylation modulate leukotriene biosynthesis in a basophil leukaemia and a mastocytoma cell line. 751 14

The effects of six recombinant human cytokines: erythropoietin, GM-CSF, G-CSF, interleukin-3, -4 and -6 on the proliferation and differentiation of a human multilineage myeloid leukemia cell line MHH 225, established from the bone marrow of an AML(M7) patient in our laboratory determined by changes in antigen expressions using monoclonal antibodies in APAAP technique were examined in liquid suspension culture. The MHH 225 cells have been growing exponentially without cytokines or conditioned media. About 90 per cent of MHH 225 cells are CD33+ CD34+ CD3- CD7- CD19- CD20- TdT- with 57.6 per cent, 28.3 per cent and 7.8 per cent of them being CD41+, glycophorin A+ and CD15+, respectively. After five days of treatment with erythropoietin, GM-CSF, G-CSF or IL-6 no change was observed in MHH 225 cell antigens expression. IL-3 (100 U/ml) induced a moderate increase in only CD13 and alpha naphthyl esterase positive cells from 6.5 +/- 1.9 per cent and 5.7 +/- 2.4 per cent in control cultures to 21.6 +/- 3.0 per cent and 19.1 +/- 2.8 per cent, respectively. On the other hand, 100 U/ml IL-4 significantly increased the number of CD13, CD15 and alpha naphthyl esterase positive cells to 48.9 +/- 5.0 per cent, 47.2 +/- 3.6 per cent and 46.1 +/- 3.0 per cent, p < 0.001, respectively. Also, 100 U/ml IL-4 decreased the number of CD41 positive cells from 57.6 +/- 2.8 per cent to only 25.9 +/- 3.6 per cent and did not change the number of CD33 or glycophorin A positive cells. The present results showed that out of the six myelopoietic growth factors tested, IL-4 was the only one to inhibit selectively the proliferation of CD33+ CD41+ leukemic megakaryoblast cells suggesting that IL-4 may have a lineage regulatory effect in favour of a myeloblastic CD33+ CD13+ CD15+ at the expense of a megakaryoblastic CD33+ CD41+ amplification in human leukemia cells and with apparently no effect on leukemic erythroblast cells. The MHH 225 cell line provides a useful tool and freely available model to scientists for studying signal transduction via IL-4 and for studies of 'lineage switch'.
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PMID:Interleukin-4 inhibits proliferation of human leukemic megakaryoblast cell line MHH 225. 752 Aug 82


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