Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulatory effects on myelopoiesis and myelogenous leukaemia cell proliferation mediated by a human T cell clone (TCC) carrying a gamma/delta receptor have been studied. MHC-unrestricted cytotoxicity could be induced in this clone by culture with IL-2 but not IL-4. Increasing concentrations of IL-2 resulted in increased lysis of natural killer (NK)-susceptible target cells but lysis of NK-resistant targets could not be induced. Moreover, cytotoxicity on fresh chronic myeloid leukaemia cells was not measurable even after culture with 1000 U/ml IL-2. However, NK-resistant targets could be lysed when anti-receptor antibodies (OKT3 or TCR-delta 1) were added to the assay. Clone 290-2 cells secreted lymphokines potentially inhibitory for myelopoiesis (TNF-alpha, IFN-gamma), and their supernatants could inhibit optimally stimulated granulocyte/macrophage colony formation by normal bone marrow. Moreover, 290-2 cells prevented the consistently observed IL-3-stimulated enhancement of proliferation of CML cells, although even IL-3-pretreated leukaemic cells were still resistant to lysis by this clone. Thus, cells of this type, even when not directly cytolytic, could have a role in the regulation of myeloid cell growth.
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PMID:Regulation of normal myelopoiesis and chronic myelogenous leukaemia cell proliferation through a non-cytotoxic mechanism by a gamma/delta T cell clone. 253 Jan 64

Recently, we reported that recombinant interferon-alpha (rIFN-alpha) can induce hematologic remissions and cytogenetic improvement in newly diagnosed Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) patients. Although IFN-gamma is a structurally distinct molecule, this agent suppresses in vitro hematopoietic progenitor cells in a fashion similar to that of IFN-alpha. Therefore, we initiated a study of rIFN-gamma at doses of 0.25 to 0.5 mg/m2/d intramuscularly in patients with Ph-positive benign-phase CML. Twenty-six of 30 patients entered in the study were evaluable. Six patients have achieved a complete hematologic response; four, a partial hematologic response. The median follow-up period of patients who are in complete remission is 7.5 months (range, 5 to 12 months). No relapses have occurred among the complete responders. So far, five patients have had cytogenetic improvement with emergence of 5% to 45% diploid cells in the bone marrow. Fever and flulike symptoms were the most common side effects, with partial tolerance often developing after about 1 week. The majority of patients tolerated therapy with minimal change in performance status. In conclusion, rIFN-gamma has demonstrated clinical activity in CML. On the basis of these observations and the in vitro synergistic growth-inhibitory effects of IFN-alpha and IFN-gamma, we have started trials of combination IFN therapy in CML patients.
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PMID:Therapy of chronic myelogenous leukemia with recombinant interferon-gamma. 311 39

Using cell culture studies specific in-vitro characteristics have been reported for Philadelphia chromosome positive myelogenous leukemia (Ph+ CML) and for juvenile chronic myelogenous leukemia (JCML) previously. We performed cell culture studies in four patients with chronic myelomonocytic leukemia (CMML) and demonstrated the following in-vitro features: excessively increased circulating CFU-C, while BFU-E and CFU-mix were either moderately increased or not detectable; CFU-C colony formation from CMML mononuclear cells (MNC) without addition of exogenous colony stimulating activity (CSA), even after depletion from adherent cells; failing inhibition of CMML MNC on normal BFU-E colony formation. These in-vitro characteristics point to CMML as a distinct entity. In two CMML-patients investigated CFU-C proliferation appeared to some extent inhibited by the addition of IFN-alpha, IFN-gamma and TNF-alpha to cell cultures.
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PMID:Colony growth characteristics in chronic myelomonocytic leukemia. 316 85

Interferons (INF) are glycoproteins with protean antiviral, immunomodulator, and antiproliferative actions. In Haematology, IFN-alpha is the most widely used. Diffusion into the spleen, bone marrow and liver is good. Hairy cell leukemia is probably the malignant blood disorder which responds best to IFN. At some time during their treatment, nearly 90% of the patients require IFN. Treatment initiation is indicated when pancytopenia (polynuclear neutrophils below 1 x 10(9)/L) develops or in case of a very voluminous spleen. IFN-alpha 2a, 2b and 2c are active (leukocyte IFN is used less often, as is IFN-beta; IFN-gamma is ineffective). The standard dose is 3 x 10(6) U, three times a week for 12 weeks. Smaller doses and maintenance treatment is sometimes proposed. Haematological remission occurs in almost all cases, if not a misdiagnosis must be considered (villous lymphocyte lymphoma). Relapse usually occurs at the end of treatment, but sensitivity to IFN is not altered and final survival is improved. Nearly 90% of the patients are alive at 4 years. Although IFN is active in chronic myeloid leukemia, research in this area continues. Clinical trials have reported haematologic relapse in 90% and complete cytogenetic response in 15 to 35% of the patients. The effect on Ph+ cells is not observed with classical chemotherapies. Initial dose is generally 5 x 10(6) U/m2/day. High doses are not always well tolerated, but cytogenetic response is only seen in patients in haematologic and cytopenic remission. IFN therapy improves survival over classical treatments (median 62 versus 39 months). Survival is better after good cytogenetic response or complete remission. Combined chemo-IFN therapy is currently under study in an attempt to improve cytogenetic response. In terms of the molecular biology however, residual disease is almost always present and relapse is frequent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Interferons. Treatment of malignant hemopathies with interferons]. 751 80

Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established.
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PMID:[Cytokines in the treatment of blood diseases]. 754 26

Soluble class I molecules (sHLA-ABC) were measured by an enzyme-linked immunosorbent assay (ELISA) in plasma samples of 13 patients with chronic-phase Ph1-positive chronic myelogenous leukemia (CML). The patients were treated once daily with interferon (IFN) s.c. at a dosage of 4 x 10(6) IU/m2 IFN-alpha-2b or in combination with 50 micrograms IFN-gamma. Measurements were performed before 2, 4, 6, 8, 24, 48, and 72 h after the start of treatment and thereafter every 2-4 weeks. Baseline sHLA-ABC levels were within normal limits (mean 22.1 +/- 8.8 mg/l). An initial decrease of sHLA-ABC (mean 3.2 +/- 2.7 mg/l) was seen in all patients during the first 2-8 h of IFN treatment. Thereafter, sHLA-ABC levels increased steadily reaching maximum values within 2-5 weeks. The overall increase was 12.7 +/- 12.4 mg/l. During the following 2-4 months of IFN treatment sHLA-ABC decreased to near baseline levels in 12 of 13 patients. No difference was detected between IFN-alpha and IFN-alpha plus IFN-gamma treatment. beta 2-Microglobulin values were measured in 8 patients and were found to be correlated to sHLA-ABC concentrations (r = 0.48).
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PMID:Soluble HLA class I and beta-2-microglobulin plasma concentrations during interferon treatment of chronic myelogenous leukemia. 786 33

Donor marrow transplantation can cure chronic myelogenous leukemia (CML). Unfortunately, the procedure is associated with severe complications and is limited to the minority of potential recipients with suitably matched donors. Autologous marrow transplantation using negative selection approaches such as incubation with gamma interferon (IFN-gamma) can produce cytogenetic and clinical remissions, but they are often associated with recurrent evidence of leukemia. A primitive progenitor population can be separated from normal human marrow on the basis of morphologic characteristics and cell surface antigen expression. Cell populations with similar morphologic and phenotypic characteristics obtained by positive selection from the marrow of patients with CML appear to be benign. Benign primitive and committed progenitors selected in this fashion can be expanded ex vivo when cultured in a "Transwell" system which physically separates hematopoietic cells from stromal feeder layers. Positive selection and ex vivo cultivation of benign progenitors from CML marrow may provide a source of hematopoietic stem cells suitable for autologous marrow transplantation. Autologous natural killer (NK) cells obtained from the peripheral blood of patients with CML are of benign origin and have antileukemia activity. Interleukin 2 (IL-2) activated autologous NK cells may be used in post-transplant cellular therapy to prevent recurrence of CML.
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PMID:Chronic myelogenous leukemia: in search of the benign hematopoietic stem cell. 790 18

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
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PMID:[Interferon-alpha, beta, gamma]. 799 28

Cell membrane fluidity (CMF) and transferrin receptor (Tf-R) expression were investigated in K562 cells, a human chronic myelocytic leukemia cell line, treated by gamma-interferon (IFN-gamma). CMF was increased using spin-labeled electron spin resonance techniques, and Tf-R expression was measured by flow cytometric analysis with an EPICS-750 flow cytometer/cell sorter. Treatment of K562 cells in suspension culture with IFN-gamma for as long a time as 6 hr caused an increase in CMF, and then returned to the level of control cells at 12 hr. Conversely, by 24 hr after the beginning of treatment, the rigidity of CMF was increased. Thus, the changes of IFN-gamma-induced CMF was biphasic. While the early change of CMF is related to signal generation and transmission, the later change may reflect changes in lipid compositions and/or cytoskeletal complexes of the plasma cell membrane. A significant increase of Tf-R after 6 hr and 24 hr in number was obtained by treatment of K562 cells with IFN-gamma, but at 12 hr the number of Tf-R did not differ from the control. These results suggested that the early phase of upregulation of Tf-R induced by IFN-gamma was caused by increased CMF, and the late phase of upregulation of Tf-R was due to increased rigidity of CMF. In conclusion, the state of CMF associated with a certain receptor expression in cells is not rigid and can be modulated to some extent by exogenous influences. This may open possibilities of some adjuvant therapeutic measures in malignant diseases by increasing the antigenicity of tumor cells.
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PMID:Cell membrane fluidity in K562 cells and its relation to receptor expression. 799 58

Interferon (IFN) is widely employed in the therapy of chronic myelogenous leukaemia because of its ability to exert the antiproliferative activity on leukaemic haematopoietic progenitors and for the expression for IFN-alpha receptors by peripheral blood leukaemic cell surfaces. There is no difference between recombinant IFN alpha 2b and alpha 2a regarding their efficacy in the treatment of Ph-positive CML patients. Either no randomized studies or the randomized ones show a superior effectiveness of IFN given as single agent in the induction treatment to that one of chemotherapy regarding the complete cytogenic response percentage. The ability of IFN-gamma to induce the expression of adhesion molecules such LFA 1 and ICAM 1 on peripheral blood leukaemic cell surfaces may suggest its use in the induction therapy of CML patients. Other than, a superior effectiveness of combined therapy including interferon and chemotherapy agents compared to chemotherapy alone has also been found. Finally no large series of trials to study the IFN efficacy both as second line treatment and maintenance therapy have been carried out.
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PMID:Interferon and chronic myelogenous leukaemia. 854 46


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