Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferons are new and effective agents in the treatment of various haematological neoplasias. Alpha-interferon (natural or recombinant) has a high efficacy (90% response rate) in hairy cell leukaemia. Complete remissions are, however, rare and definite cure of the disease is unlikely. Alpha-interferon induces haematological remissions in about two thirds of patients with chronic myeloid leukaemia and leads to a reduction in Philadelphia chromosome in about 40% of patients. It is uncertain, however, whether this treatment will actually prolong the life of these patients as compared with conventional treatment. Alpha-interferon has a beneficial effect in some patients with low malignant non-Hodgkin lymphomas (in particular follicular lymphomas). The response rate in myeloma is rather small (20%). Gamma-interferon is not effective in hairy cell leukaemia, non-Hodgkin lymphoma and myeloma. It is, however, of some efficacy in chronic myeloid leukaemia (the response rate in lower than with alpha-interferon) and possibly has some effect in patients with acute myeloid leukaemia and myelodysplastic syndromes. The toxicity of interferons (alpha and gamma) consists of an influenza-like syndrome during the first days of treatment. Low doses of alpha-interferon show virtually no long-term toxicity. However, bone and muscular pain is sometimes dose-limiting with intermediate doses (5 to 15 million units) of alpha-interferon.
 ...
PMID:[Interferon therapy in hematologic neoplasms]. 245 54

Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.
 ...
PMID:Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia. 249 71

The natural killer (NK) cell activity of the blood and marrow was studied in patients with acute myelogenous leukemia (AML). NK activity of the cells from blood and marrow was significantly decreased in AML to three target cell lines. Both binding and killing capacities of the effector cells were deeply depressed in the blood as well as in the marrow at single cell assay. Surface phenotypic analysis showed a significant decrease in CD 11+ cell subsets, but not in CD 16+ or Leu-7+ cells, in both blood and marrow cells from AML. A significant decrease of large granular lymphocytes (LGL) was also displayed in these samples at morphological examination. The effector cells from AML patients poorly responded to interferon stimulation in NK cytolysis. Taken together, a decrease in CD 11+ cell population with LGL morphology appeared to be responsible for the impaired NK activity in patients with AML.
 ...
PMID:Depressed natural killer (NK) function in blood and marrow is related to the decrease in CD 11+ cells in acute leukemia. 257 13

Bone marrow cells from 15 patients with myelodysplastic syndromes and 2 with acute myeloid leukemia were incubated in vitro with all-trans-retinoic acid (RA), 1,25-dihydroxy vitamin D3 (D3), cytosine arabinoside (ara-C) and alpha-interferon (IFN). 3H-thymidine incorporation (3H-TdR), differentiation and clonal growth were studied. D3 was found to be the most effective inducer of differentiation and differentiation was correlated with a decreased 3H-TdR. Differentiation with one of the inducers was significantly correlated to differentiation with any of the other inducers. Patterns of differentiation and spontaneous and D3-induced 3H-TdR were used to divide the patients into 3 different groups. In the first group, 5 patients with extremely low spontaneous 3H-TdR and differentiation in combination with a slightly increased 3H-TdR after induction differed from all other patients by a higher percentage of bone marrow blast and a more pronounced pancytopenia. The two other groups had a high spontaneous 3H-TdR but differed with respect to the D3-induced differentiation which was absent in one group (n = 6) and present in the other (n = 5). The two groups showed no difference in the clinical features.
 ...
PMID:Effects of retinoic acid, 1,25-dihydroxyvitamin D3, cytosine arabinoside and alpha-interferon on bone marrow cells from patients with myelodysplastic syndromes. 261 68

Recent reports have described the expression of myeloid cell surface antigens on cells of small cell carcinoma of the lung (SCCL). In order to confirm and extend these findings, we have examined by cytofluorography a large panel of well-characterized cell lines derived from SCCL tumors for the expression of several myeloid cell-associated antigens, some of which were not examined in previous reports. In addition, we have studied the expression of Classes I and II HLA antigens on these SCCL cell lines. Finally, we examined the effect of gamma-interferon on the expression of several cell surface markers and on proliferation of SCCL cells. We have found that several SCCL cell lines expressed a Mr 55,000 polypeptide antigen, My23, previously found only on monocytes and monocytic leukemia cells. In addition, the cell lines studied expressed another antigen, defined by monoclonal antibody AML-1-99, which is associated with monocytes and hematopoietic stem cells. We confirmed previous studies that the Leu-7 antigenic determinant is expressed on SCCL cells but observed only minimal or absent binding of monoclonal antibody OKM1 to most cell lines. Class I HLA antigens were present on eight of nine lines examined while Class II HLA was expressed on three of nine lines. Gamma-Interferon decreased the proliferative rate of all lines examined. However, this lymphokine was capable of inducing Class I HLA on several lines. The effect of gamma-interferon on other cell surface antigens was variable. These studies confirm that some myeloid cell-associated antigens are expressed on cultured SCCL lines and, additionally, show that their expression can be modulated by immune interferon. Determining the significance of finding myeloid cell-associated antigens on SCCL cells will require further study.
 ...
PMID:Expression of myeloid and major histocompatibility antigens on small cell carcinoma of the lung cell lines analyzed by cytofluorography: modulation by gamma-interferon. 300 87

A proportion of blasts from five of 10 cases of AML expressed receptors for IL-2 (IL-2R) when tested directly ex-vivo with monoclonal antibodies against the receptor. After in-vitro stimulation with various agents including TPA, gamma interferon and colony stimulating factor, the purified blast cells of all cases of AML tested (10 of 10) showed high levels (50-90% cells positive) of IL-2R expression. Granulocytic cells from the promyelocyte stage onwards lacked IL-2R both before and after in-vitro stimulation. In contrast, leukaemic promonocytes and normal peripheral monocytes expressed IL-2R both before and after stimulation. The receptors were detected with two different monoclonal antibodies (anti-Tac and 4H3--both IgG 2a antibodies) by indirect rosetting. In selected experiments, results were confirmed by fluorescence microscopy and by the APAAP technique. Normal monocytes possessed only small amounts of IL-2R since positivity was clearly detectable only by the indirect rosette assay. Irrelevant IgG 2a first-layer and second-layer-only controls were always negative. The endogenous nature of the IL-2 receptors was demonstrated by re-expression after capping and shedding. That the antigens detected were true IL-2R was confirmed by the fact that monoclonal antibody staining was blocked by recombinant IL-2. The restricted expression of IL-2R on early granulocytic and on monocytoid cells raises the possibility that IL-2 is important in the proliferation of these cell types.
 ...
PMID:Certain myeloid cells possess receptors for interleukin-2. 302 33

The expression of HLA-DR antigen by highly enriched human monocytes cultured in serum free medium was found to be markedly elevated by human recombinant gamma interferon (IFN-gamma). This effect was maximal after 48 h in culture with 300 mu/ml IFN-gamma. Class I MHC antigen also increased with IFN-gamma treatment. By contrast, binding of a myeloid-specific monoclonal antibody, AML-2-23, was dramatically decreased by IFN-gamma. The augmentation of MHC antigens was not ablated by an immunosuppressive concentration (2 X 10(-7) M) of the glucocorticoid dexamethasone (DEX). In fact, both the enhancement of Class I and Class II MHC antigen expression and the suppression of AML-2-23 antigen by IFN-gamma were often more profound in the presence of DEX. IFN-gamma treatment also resulted in elevated monocyte effector function, as measured by antibody dependent cellular cytotoxicity (ADCC). This functional activation was not inhibited by DEX. On the contrary, DEX slightly augmented IFN-gamma effects on ADCC. This contrasts with other reports that glucocorticoids inhibit monocyte responsiveness to lymphokines, and suggests that the interplay between lymphokines and the glucocorticoid hormones may be more complex than previously thought.
 ...
PMID:Glucocorticoid enhances gamma interferon effects on human monocyte antigen expression and ADCC. 309 77

We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia--one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and gamma-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-1 of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML.
 ...
PMID:Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts. 310 70

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.
 ...
PMID:Heterogeneity in acute undifferentiated leukemia. 319 52

The promyelocytic cell line HL-60 could be induced to differentiate into morphologically and functionally mature monocytoid cells (up to 20%) following exposure to the Chinese herb Clerodendron Fragrans (1 mg/ml). This effect was time dependent and appeared to work synergistically with interferon-r in this promotion of differentiation. Our study suggests that Clerodendron Fragrans has potential therapeutic value for the treatment of certain acute myelocytic leukemia putatively caused by a block in the myeloid differentiation process.
 ...
PMID:In vitro induction of differentiation in HL-60 leukemic cell line by clerodendron fragrans. 324 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>