Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease of the elderly which can present in one of three stages; benign, intermediate or advanced. The molecular events governing the progression of CLL are poorly understood. In order to develop model systems for predicting the aggressiveness of leukemic clones in CLL, in vivo transplantation of SCID mice with CLL cells, and the in vitro growth of CLL cells on mouse and human stromal layers, were investigated. Bone marrow or peripheral blood cells from 40 patients at different stages of CLL were transplanted into 172 immune-deficient SCID mice. Thirty-five percent of SCID mice injected with CLL cells were positive for the presence of human DNA by Southern blot or PCR analysis. The most frequently involved sites were the spleen, lung, kidney and bone marrow, at levels corresponding from 0.1 to 10 percent human DNA. Thrice-weekly intraperitoneal injections of IL-2, alone or in combination with IL-7, did not increase the level of human cell engraftment. SCID mice developed endogenous thymic lymphomas at an incidence of 10-33 percent, a rate that was not increased by CLL cell transplantation. In vitro, CLL cells were able to proliferate for 9 weeks on human stromal layers supplemented with CM (conditioned media from a culture of the human bladder carcinoma cell line 5637), but failed to thrive on the murine stromal cell line MTE cultured either in CM or autologous serum. FACS analysis revealed that 81 percent of proliferating cells on human stromal layers carried the CD5 cell surface marker, identifying them as CLL cells. Previously EBV-negative CLL cells became EBV-positive after 9 to 12 weeks in culture. The results of this study provide a firm foundation for the development of in vivo and in vitro model systems for the study of human CLL.
Leukemia 1996 Aug
PMID:Engraftment of human chronic lymphocytic leukemia cells in SCID mice: in vivo and in vitro studies. 870 47

Mice infected with Friend Leukemia Virus (FLV) rapidly develop erythroleukemia and severe immune deficiency which resembles human AIDS. We have reported that mice infected with a lethal dose of FLV can be 100% cured by 150 cGy total body irradiation (TBI). This curative effect was associated with restoration of cellular immunity which was compromised by the virus. This restoration may result from activation of the IFN-gamma system and IL-2 production. Our research work further demonstrated that no spleen focus-forming virus (SFFV) specific mRNAs, no 6.0kb SFFV fragments and SFFV envelope glycoproteins were detectable in FLV-infected mice treated with low dose TBI. Predicated on our report, del Regato has initiated clinical trials to treat AIDS patients with low dose TBI. The preliminary results are encouraging and the study is continuing. We have also studied the effects of low dose TBI on the expression of the P53 gene. The results show loss or inactivation of P53 tumor suppressor genes in FLV-infected mice, but P53 expression was restored in FLV-infected mice treated by low dose TBI. It is intriguing to speculate that in the curative effect of low dose TBI on mice infected with retrovirus, the P53 tumor suppressor gene may play an important role. It would be of interest to see if this type of treatment, which was well tolerated by mice, would be beneficial in other types of virally induced disease, including AIDS.
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PMID:Curative effect of split low dosage total-body irradiation on murine AIDS induced by Friend virus: the results and the possible mechanism. 874

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.
Leukemia 1996 Sep
PMID:Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A. 875 70

IL-12 is a novel cytokine with interesting features regarding its potential usefulness in peripheral blood stem cell transplantation and leukemia immunotherapy. We used cryopreserved leukemia cells of 18 patients with acute myelogenous (n= 14) or lymphocytic (n= 4) leukemia to investigate the effect of IL-12, alone or in combination with IL-2, on the cytolytic activity of NK cells against human leukemia targets. Effector cells were peripheral blood mononuclear cells from healthy donors which were depleted from CD3+ T cells by immunomagnetic separation. CD3-negative effector cells (mainly CD56+ NK cells) were treated for 24 h with various concentrations of IL-2 (100 U/ml to 1000 U/ml) and IL-12 (1 U/ml to 100 U/ml). Cytotoxicity was measured in a 4 h 51Cr-release assay. Whereas a two-fold enhancement of cytotoxic activity was observed after incubation with optimal doses of IL-2 or IL-12, the combination of both cytokines (500 U/ml IL-2, 100 U/ml IL-12) increased the lytic activity more than six-fold. This effect was accompanied by increased expression of cellular adhesion molecules (CD2, CD18) and CD25 on CD56+ effector cells. Of 18 leukemias investigated, five were completely resistant to lysis by effector cells activated with IL-2 or IL-12 alone. In three of these five cases, however, high cytolytic activity was observed after coincubation with IL-2 and IL-12. In comparison to allogeneic NK cells, autologous cells of three patients in remission demonstrated significantly lower cytotoxic activity. No killing of nonmalignant cells (PHA blasts) by allogeneic NK cells was observed. Our data demonstrate that IL-12 can enhance or even induce MHC-unrestricted cytotoxicity of IL-2-activated allogeneic natural killer cells. Since IL-12 has also been shown to have stem-cell mobilizing capacities, it could be used for the recruitment of both stem cells and antileukemic effector cells in the context of peripheral blood stem cell transplantation.
Leukemia 1996 Nov
PMID:High lytic activity against human leukemia cells after activation of allogeneic NK cells by IL-12 and IL-2. 889 79

Leukemic cells from a 45-year-old male patient with a CD3+, CD56+, CD57+, CD7+ acute lymphoblastic leukemia were cultured in vitro in the absence of any added growth factor for up to 6 years and a continuous lymphoblastoid cell line (NOI-90) was established. NOI-90 cells have the same phenotype and karyotype as initial leukemic cells. Southern blot of DNA from NOI-90 cells showed that TCRbeta, TCRgamma, and J(H) were in germ line. Two and 25% of NOI-90 cells were positive when stained with the IOT14 and 7G7/B6 moAbs, which recognize the CD25 molecule (IL-2R alpha chain); moreover, 4% and 13% of the cells were positive when stained with the TU-27 and mik beta3 moAbs which recognize the CD122 molecule (IL-2Rbeta chain). Equilibrium binding experiments with radiolabelled IL-2 revealed the presence of a small number of high affinity IL-2R on both fresh and continuously growing cells. Media conditioned by NOI-90 cells could induce proliferation of an IL-2-dependent cell line and this IL-2 activity could be detected by a sensitive immunoenzymatic assay using antibodies recognizing distinct epitopes of IL-2. Moreover, IL-2 activity could be adsorbed by immunoaffinity on anti-IL-2 polyclonal purified IgG and the retained molecule displayed a m.w. of 14.5 kDa in SDS-PAGE. In addition, IL-2 immunoreactive molecules could be revealed in the cytoplasm of the cells. Finally, IL-2 fixed on the cell membrane could be detected by indirect immunofluorescence. Although added IL-2 could not induce cell proliferation, monoclonal antibodies against CD25, CD122 and IL-2 could specifically inhibit spontaneous cell proliferation in a dose-dependent manner. NOI-90 cells failed to demonstrate any cytotoxic activity against the K-562, Raji or Daudi cells. These findings indicate that NOI-90 cells are of non-T, non-B, origin lacking NK activity but proliferate under an autocrine pathway which involves, at least partly, the IL-2/IL-2R system.
Leukemia 1997 Feb
PMID:Autocrine IL-2-dependent growth of a newly established CD3+, CD16-, CD56+, CD57+, J(H)-, TCRbeta-, TCRgamma- leukemia cell line (NOI-90). 900 88

Human T cell leukemia/lymphotropic virus (HTLV) is a complex 9 kb human retrovirus with at least eight alternatively spliced mRNAs expressed from the 3' or pX region of the genome. These mRNAs allow for the expression of novel proteins from the previously recognized pX open reading frames I and II in addition to Tax, Rex and p21rex encoded from orf III and IV. These alternatively spliced messages have been detected using reverse-transcriptase polymerase chain reaction (RT/PCR) amplification in HTLV-I-transformed T cell lines as well as in peripheral blood mononuclear cells (PBMC) from infected patients with and without disease. To gain insight into the role of these alternatively spliced mRNAs in pathogenesis, we developed a semi-quantitative non-PCR-based RNase protection assay to detect and quantitate their presence in HTLV-I-infected cells. Analysis of RNA from HTLV-I-infected cells established from patients with adult T cell leukemia (ATL) as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and both IL-2-dependent and IL-2-independent HTLV-I-infected cell lines by RNase protection has confirmed the existence of all of the alternatively spliced messages in each cell line analyzed. However, the relative quantity of each message was significantly different among these lines suggesting that splice site utilization is an important viral regulatory pathway.
Leukemia 1997 Jun
PMID:Differential expression of alternatively spliced pX mRNAs in HTLV-I-infected cell lines. 917 42

We established a factor-independent acute myeloid leukemia cell line, designated Ei501. The line has been growing in RPMI 1640 media for 18 months and can be maintained without addition of growth factors. Ei501 is positive for myeloperoxidase and negative for esterase and PAS. Cytogenetic analysis revealed the FAB M3 associated t(15;17) translocation and a translocation of the chromosomes 7 and 8: 46 XX, -7, +t(7;8)(q32;q13), t(15;17)(q22;q12). This karyotype was confirmed by fluorescence in situ hybridization. Ei501 cells express AML-associated surface markers such as CD13, CD33 and CD38. Although 42% of the patient's blast cells were CD34-positive, the line lacks surface expression of CD34. Furthermore the line has a number of characteristics which are detectable in blasts from AML patients, such as surface adhesion molecules, cytokines such as TGF-beta, cytokine receptors such as the IL-2 receptor beta and gamma chains or the IL-4 receptor and the genes for the transcription factor wt-1 (Wilms' tumor gene) and for the proto-oncogene bcl-2, both shown to be present in the majority of patients with AML. Additionally the line can be used as target in cytotoxicity assays using IL-2 activated cytotoxic lymphocytes as effector cells. In conclusion, besides a rare karyotype the Ei501 cell line has several features common in AML, and may therefore be used as a model to study pathogenetic mechanisms in acute myeloid leukemia.
Leukemia 1997 May
PMID:Establishment and characterization of a new, factor-independent acute myeloid leukemia line designated Ei501. 918 Feb 96

The association between chromosomal changes and cellular growth potential was investigated in HTLV-I infected human lymphocytes. Cell lines studied include Coculture-5 (HTLV-I infected immortalized cells dependent of IL-2), Coculture-15 and -18 (semi-transformed Coculture-5 cells following cocultivation with transformed Coculture-5 cells), UV-5 (Coculture-5 cells transformed following UV irradiation), and MNNG-1 (Coculture-5 cells transformed following MNNG treatment). Immortalized cells were grown in IL-2 medium (IL-2+PHA+TPA), whereas semi-transformed and transformed cells were grown in RPMI medium. By G-band karyotyping, double band formation was seen in 3-33% of spreads at the centromeric region of chromosomes 1 and 7 to which structural abnormalities were found to cluster. The double band formation was also seen by FISH using alpha satellite DNA probe in Coculture-5 and -15 thus far examined. The ploidy of immortalized, semi-transformed, and transformed cell lines, was 4n, 4n to 2n, and 2n range, respectively. These findings suggest that chromosomal rearrangements cause abnormalities in cell division kinetics resulting in numerical and structural abnormalities of chromosomes, and render host cells growth advantage.
Leukemia 1997 Apr
PMID:Chromosome changes associated with growth potential of HTLV-I infected human lymphocytes. 920 88

The interaction between HTLV-I infected immortalized cells and transformed cells was studied. HTLV-I infected immortalized human lymphocytes (Coculture-5) dependent of IL-2 medium (IL-2+PHA+TPA) and transformed cells (UV-5) derived from Coculture-5 following UV irradiation were cocultured in equal numbers in IL-2 medium. UV-5 cells were suppressed and disappeared about 1 month in cocultivation. UV-5 cells were not suppressed in IL-2 medium. Coculture-5 cells and UV-5 cells were seeded in Transwell dishes that were separated by membrane with pores 0.4 micron in diameter and cultured in IL-2 medium. UV-5 cells were suppressed indicating that cell-cell contact was not required for the observed suppression. UV-5 cells were markedly suppressed in IL-2 medium harvested from Coculture-5 cells when recombinant interferon alpha (1000 U/ml) was added to the medium. These findings demonstrated that growth of HTLV-I infected transformed cells could be suppressed by cytokine(s) released by HTLV-I carrier lymphocytes.
Leukemia 1997 Apr
PMID:Cytokine mediated growth inhibition of HTLV-I infected transformed human lymphocytes. 920 89

In controlling retrovirus infection and replication, cell-mediated immunity (CMI) is considered to be effective. To develop a synthetic peptide vaccine capable of inducing CMI, mannan-coated liposome encapsulating 20-mer synthetic peptide, spanning the 98-117 amino acids of bovine leukemia virus (BLV) envelope glycoprotein (Env) gp51 was constructed and inoculated to BALB/c mice. The liposome induced specific delayed-type hypersensitivity, lymphocyte proliferative responses, and a weak cytotoxic lymphocyte response. The spleen cells from the immunized mice produced a large amount of IFN-gamma and IL-2, whereas they released neither IL-4 or IL-10. Mannan-coated liposome containing two kinds of peptides (the 121-140 and 142-161 regions of BLV Env gp51) also induced peptide-specific lymphocyte proliferative response and IFN-g production in C57BL/6 mice. Thus, the synthetic T-cell epitope peptide-liposome system augmented a strong Th-1 type immunity in mice.
Leukemia 1997 Apr
PMID:Peptide-based bovine leukemia virus (BLV) vaccine that induces BLV-Env specific Th-1 type immunity. 920 48


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