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)

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.
Leukemia 1993 May
PMID:In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity. 848 27

Because chemotherapy alone does not eliminate clonogenic leukemic cells, disease may recur after induction and consolidation chemotherapy. Studies of patients receiving high-dose chemotherapy supported by bone marrow or blood stem-cell transplantation suggest that immune-mediated effects of transplanted cells help control disease. This antileukemic (graft-versus-leukemia) effect represents several immune reactions. Various approaches to introduce or enhance such immune reactivity in patients with acute myeloid leukemia (AML) are being explored. There is some indication, even in older patients, that immunotherapy is better tolerated than chemotherapy, and efforts are underway to find the most effective treatment for maintaining remission after induction chemotherapy. We have developed a strategy that combines myeloablative chemotherapy with transplantation of autologous stem cells that have been cultured for 1 week in interleukin-2. Low-dose interleukin-2 is also administered for the first week after stem cell infusion. Although all patients developed side effects of fever and fatigue, even older patients tolerated this regimen well. The 3-year disease-free survival rate in a high-risk patient group transplanted in early first remission is 41 percent. Several other compounds are being investigated for their ability to enhance immune reactions after induction chemotherapy for AML. Although immunotherapy cannot eliminate overt leukemia and cytoreductive treatment is still needed initially, immunotherapy may find a place in postinduction management of AML to eliminate minimal (residual) disease or control its growth.
Leukemia 1996 Apr
PMID:Role of postinduction immunotherapy in acute myeloid leukemia. 861 64

We studied the natural killer (NK) cell activity and in vitro production of the cytokines which can enhance NK activity (interleukin-1 beta (IL-1 beta), interferon gamma (IFN gamma), and interleukin-2 (IL-2)) after stimulation in 44 patients with acute leukemia (AL) and 14 normal controls. We also studied the influence of these parameters on relapse and the relapse-free survival (RFS) (after the date of assay) of the AL patients. The NK activity and the production of cytokines in the peripheral blood mononuclear cells (PBMNC) from 16 patients at the untreated or relapsed stage as well as from 12 patients after consolidation were significantly lower than those from controls (both P<0.01), and those from the 16 patients at maintenance or off treatment were also significantly lower than those from the controls (P<0.01 or P<0.05). RFS after the date of assay of the patients in remission with NK activity above the median value was significantly longer than that of the patients below the median (P<0.05). The production of cytokines in the PBMNC from patients who showed continuous complete remission for at least 6 months was higher than that from the patients who relapsed early. These findings suggest that impaired NK cell function and cytokine production are associated with early relapse of AL regardless of remission status.
Leukemia 1996 Mar
PMID:Natural killer cell activity and cytokine production as prognostic factors in adult acute leukemia. 864 65

This work represents an update of our experience on mobilization and transplantation of peripheral blood progenitor cells (PBPC) collected during the early recovery phase after chemotherapy in patients with chronic myelogenous leukemia. The collection of Ph-negative precursor cells occurred in 13/19 (68%) patients mobilized within the first year from diagnosis and not previously treated with interferon alpha (IFN-alpha). Fourteen out of 42 patients (33%) achieved Ph-negative precursors beyond 1 year from diagnosis. Eleven patients mobilized early after diagnosis were subsequently autografted with Ph-negative precursor cells. All patients are alive in hematologic remission and five of them maintain Ph-negativity in the marrow 7-15 months post-autograft. Four patients showed recurrence of Ph-positive cells (5 to 40%) within 4 to 8 months after autografting. Two patients became progressively Ph-positive after 6 months and are now 100% Ph-positive and in stable chronic phase. In the early stage of the disease the mobilization/transplantation procedure is safe and associated with very good compliance. However, occasional restoration of Ph-negative hematopoiesis could occur up to 45 months after autograft in patients undergoing the procedure beyond 1 year from diagnosis, and highly pretreated with IFN-alpha, but most patients revert to Ph-positive hematopoiesis. In an attempt to control the Ph-negative status and to prevent cytogeneic relapse, we are currently treating autografted patients with low doses of IFN-alpha and interleukin-2 (IL-2). Whether and for how long Ph-negative status can be maintained is a matter for future observation and effort.
Leukemia 1996 Jun
PMID:Collection, analysis and transplantation of Ph-negative blood precursor cells in chronic myeloid leukemia. 864 50

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.
Leukemia 1996 Jul
PMID:In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients. 868

Previously it was established that L1210 mouse leukemia and a variety of other tumor cell types produced a soluble factor(s), designated tumor-derived recognition factor (TDRF), which synergized with interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) or lipopolysaccharide (LPS) to promote increased tumor necrosis factor-alpha (TNF-alpha) and nitric oxide synthase (NOS) mRNA synthesis by murine macrophages (M phi). Other work revealed that pretreatment of L1210 tumor targets with IFN-gamma rendered them more susceptible to NO-mediated killing by LPS-activated M phi. Now we have combined these observations to determine if pretreatment of L1210 or P815 tumor targets with IFN-gamma and/or IL-2 would augment production of TDRF to enhance M phi activation. Results confirmed that pretreatment of either L1210 or P815 targets with 200 u/ml of IFN-gamma or 1,000 u/ml of IL-2 significantly increased their susceptibility to M phi-mediated cytotoxicity owing to increased NO production. Similar pretreatment of L1210 targets with suboptimal concentrations of IFN-gamma and IL-2 in combination resulted in additive rather than synergistic augmentation of NO-mediated cytotoxicity by cytotoxic M phi. Pretreatment of L1210 targets with IFN-gamma or IL-2 alone or in combination increased the production of TDRF above constitutive levels as demonstrated by increased production of NO and induction of NOS mRNA expression by cytotoxic M phi. Thus IFN-gamma and/or IL-2 promoted increased TDRF production by tumor targets which in turn promoted M phi generation of tumor cytotoxic NO. It appears that M phi activating cytokines have a dual role in acting on certain tumor targets to augment the process of M phi activation through the increased elicitation of immunopotentiating tumor-derived soluble factor(s).
 ...
PMID:Interferon-gamma and interleukin-2 stimulate production of a soluble factor by L1210 and P815 tumor targets to promote macrophage activation. 885 3

Interleukin-2 (IL2) fused to ricin B chain (RTB) with modifications of amino acid residues in each of three galactose-binding subdomains (1alpha, 1beta and 2gamma) was expressed in insect cells, purified by immunoaffinity chromatography and reassociated with ricin A chain (RTA). The fusion toxin-bound human leukemic cells with IL2 receptors and the binding was competed with IL2 but not asialofetuin. In contrast, binding was not observed with receptor negative human cell lines, and the fusion molecule very weakly bound asialofetuin (Kd= 10(-6)M), indicating lectin-deficient RTB. The IL2-lectin-deficient RTB-RTA intoxicated IL2 receptor bearing cells as well as ricin or IL2-wild-type RTB-RTA. While ricin and IL2-wild-type RTB-RTA were equally toxic to receptor negative cell lines, the IL2-lectin-deficient RTB-RTA was two-two and one half logs less cytotoxic to these cell lines. The sensitivity of receptor-positive cells to the lectin-deficient fusion protein suggests that high avidity intracellular galactose binding may not be required for ricin intoxication, at least in the case of IL2 receptor-targeted molecules. Furthermore, the potent selective cytotoxicity of the fusion protein suggests that the IL2-lectin-deficient RTB-RTA and similar ricin fusion molecules directed against other leukemic cell surface receptors provide a novel class of fusion toxins for therapy of human leukemias.
Leukemia 1997 Jan
PMID:IL2 fused to lectin-deficient ricin is toxic to human leukemia cells expressing the IL2 receptor. 900 14

The effects of retinoic acid (RA) on the cell growth and expression of interleukin-2 (IL-2) receptors (IL-2R alpha/p55, Tac, CD25) by the human T lymphotropic virus type I (HTLV-I)-positive T cell lines, HUT102 and ATL-2 were investigated. Incubation of these cells for 48 h with either 13-cis retinoid acid (13-cis RA) or all-trans retinoic acid (ATRA) resulted in marked inhibition of cell growth, determined by 3H-thymidine incorporation, and in down-regulation of CD25 expression, determined by flow cytometry. Four HUT102 cell clones were established by limiting dilution, and 13-cis RA was shown to inhibit cell growth and CD25 expression in three of these clones (HUT102-M5, -M6 and -M7), but not in the fourth (-M8). RA did not induce growth inhibition or down-regulation of CD25 in the HTLV-I-negative T cell lines (Jurkat and MOLT-4) and in normal lymphocytes that had been stimulated with phytohemagglutinin or phorbol 12-myristate 13-acetate. We have shown that RA markedly inhibited both the cell growth and the expression of CD25 in some HTLV-I-positive T cell clones, but not in normal lymphocytes. These results suggest that RA may be suitable for the treatment of patients with adult T cell leukemia (ATL).
Leukemia 1997 Mar
PMID:Inhibition of proliferation and CD25 down-regulation by retinoic acid in human adult T cell leukemia cells. 906 80

Despite the presence of tumor antigens, the paucity of clinically significant T-cell mediated immune responses against human tumors is striking. This may, in part, be because of the inability of cancer cells to function as efficient antigen-presenting cells. For full activation, T cells must receive two signals delivered by antigen-presenting cells. The first is antigen-specific and is delivered by presentation of antigenic peptide by the major histocompatibility complex molecules to the T-cell receptor. This signal, although necessary, is in itself insufficient to mediate T-cell activation, cytokine release, and subsequent T-cell proliferation and function. For full T-cell activation, T cells require delivery of a secondary, costimulatory signal, such as that delivered by members of the B7 family to their receptor on the T-cell, CD28. Delivery of an antigen signal in the absence of costimulation does not result in productive immunity, but rather in anergy, a state of antigen-specific T-cell nonresponsiveness. To induce T-cell proliferation against B-cell malignancies, the tumor cell must first be induced to express B7 or the tumor antigen must be presented by an efficient antigen-presenting cell. Simple expression of B7 on the tumor cell alone, however, cannot reverse anergy. Reversal of anergy is a complex process involving stepwise repair of the T-cell defect and can be accomplished by prolonged exposure to interleukin-2, signaling through the CD2 pathway, followed by antigen presentation with B7-mediated costimulation. Successful immunotherapeutic strategies in the B-cell malignancies will likely require steps to reverse established anergy in the tumor-bearing host as well as effective tumor-antigen presentation.
Leukemia 1997 May
PMID:Biologic response modifiers in acute lymphoblastic leukemia. 917 80

Placebo-controlled and/or historically controlled trials have shown that granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance neutrophil recovery rates and occasionally reduce the rate and duration of infection. Some data appear to support an advantage with GM-CSF in reducing the incidence of fungal infections. Immunomodulation with cytokines such as interferon or interleukin-2 may prove to be of benefit in the management of acute leukemia when used in combination or sequence with chemotherapy.
Leukemia 1997 May
PMID:Use of cytokines in the treatment of acute lymphoblastic leukemia. 917 81


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