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)

Glycation, oxidation, and nonenzymatic browning of protein have all been implicated in the development of diabetic complications. The initial product of glycation of protein, fructoselysine (FL), undergoes further reactions, yielding a complex mixture of browning products, including the fluorescent lysine-arginine cross-link, pentosidine. Alternatively, FL may be cleaved oxidatively to form N(epsilon)-(carboxymethyl)lysine (CML), while glycated hydroxylysine, an amino-acid unique to collagen, may yield N(epsilon)-(carboxymethyl)hydroxylysine (CMhL). We have measured FL, pentosidine, fluorescence (excitation = 328 nm, emission = 378 nm), CML, and CMhL in insoluble skin collagen from 14 insulin-dependent diabetic patients before and after a 4-mo period of intensive therapy to improve glycemic control. Mean home blood glucose fell from 8.7 +/- 2.5 (mean +/- 1 SD) to 6.8 +/- 1.4 mM (P less than 0.005), and mean glycated hemoglobin (HbA1) from 11.6 +/- 2.3% to 8.3 +/- 1.1% (P less than 0.001). These changes were accompanied by a significant decrease in glycation of skin collagen, from 13.2 +/- 4.3 to 10.6 +/- 2.3 mmol FL/mol lysine (P less than 0.002). However, levels of browning and oxidation products (pentosidine, CML, and CMhL) and fluorescence were unchanged. These results show that the glycation of long-lived proteins can be decreased by improved glycemic control, but suggest that once cumulative damage to collagen by browning and oxidation reactions has occurred, it may not be readily reversed. Thus, in diabetic patients, institution and maintenance of good glycemic control at any time could potentially limit the extent of subsequent long-term damage to proteins by glycation and oxidation reactions.
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PMID:Decrease in skin collagen glycation with improved glycemic control in patients with insulin-dependent diabetes mellitus. 190 67

A patient whose leukaemic cells carried the rare t(7;11)(p15;p15) was diagnosed as having acute myelomonocytic leukaemia (AML-M4), and supports the association of this specific translocation with forms of acute myeloid leukaemia showing differentiation. Blast phase chronic myeloid leukaemia was excluded by lack of involvement of the ABL and BCR genes. Chromosome in situ hybridization studies showed that both the HRAS1 and INS genes were present on the terminal part of chromosome 11p which was translocated to chromosome 7p. Neither HRAS1 nor INS were structurally rearranged. Field inversion gel electrophoresis showed that a 400 kb fragment encompassing HRAS1 was structurally entire in leukaemic DNA. Because the INS gene, which was also translocated, is probably located proximal to HRAS1 on chromosome 11p, it is unlikely that HRAS1 was near the chromosome 11 breakpoint or involved in this leukaemia.
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PMID:HRAS1 and INS genes are relocated but not structurally altered as a result of the t(7;11)(p15;p15) in a clone from a patient with acute myeloid leukaemia (M4). 271 71

The percentage of total 125I-labeled insulin specifically bound to lymphoblasts was measured in 46 children with leukemia. Among 35 children with newly diagnosed acute lymphoblastic leukemia (ALL), specific insulin binding ranged from 0.09 to 14.8% per 10(6) blasts. A lower level of insulin binding was correlated with T-cell surface markers (P less than 0.003), higher hemoglobin level (P less than 0.005), presence of a mediastinal mass (P less than 0.01), lower glucocorticoid receptor level (P less than 0.02), higher platelet count (P less than 0.04), age less than 2 or greater than 10 yr (P less than 0.05), white blood cell count greater than or equal to 100 X 10(3)/mm3 (P less than 0.06) and higher labeling index (P less than 0.07). It was not correlated with the presence of central-nervous-system disease, FAB classification, or sex. With a follow-up of 24 to 33 + months, insulin binding was not correlated with treatment outcome. Six patients with relapsed ALL and three with acute nonlymphoblastic leukemia showed insulin binding levels similar to those in newly diagnosed ALL patients. Blasts from one patient with B-cell ALL and one with chronic myelogenous leukemia were characterized by lower insulin binding, while lymphoblasts from a patient with T-cell lymphoma bound insulin at marginally detectable levels. In vitro studies with IM-9, NALM-1 and NALM-16 cell lines showed that changes in insulin binding caused by dexamethasone treatment were not correlated with hormone-induced cell death. Although study of insulin binding by malignant lymphoid cells may be important in understanding the biology of leukemic cells, it does not appear to have any obvious clinical utility.
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PMID:Clinical and biologic correlates of insulin binding by leukemia lymphoblasts. 389 3

GH, LH, insulin and glucagon patterns were studied in the peripheral leukocytes of normal subjects (granulocytes and lymphocytes separated on a Ficoll-Hypaque gradient) and leukaemic patients (CML, AML, CLL, and ALL), using a double antibody RIA on whole cells. The uptake of 125I-labelled insulin and GH by these cells was also assessed. The results showed that in leukaemia, particularly CLL, ALL and AML, though not in CML, there was a constant reduction in hormone values, plus depressed GH and insulin uptake. The only exceptions were glucagon and insulin in CML, and LH in CLL, since their concentrations were normal or clearly enhanced. The data are seen as an expression of a membrane receptor block extending to several hormones with structural differences (protein, steroid, T3 and T4), capable of altering the ability of leukaemic cells to respond to ordinary factors modulating their differentiation, functional activity, and the expansion of the corresponding stem cell compartment.
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PMID:[Behavior of the principal protein hormones in normal and leukemic leukocytes]. 630 18

Insulin binding activity and its changes in relation to terminal differentiation were studied in the HL60 human promyelocytic cell line, and in myeloid cells from both normal bone marrow and chronic myeloid leukemia (CML) patients. After treatment with dimethylsulfoxide, the HL60 line began to differentiate into more mature myeloid cells. Treated and untreated HL60 cells were found to possess specific insulin receptors with characteristics similar to those of monocytes and granulocytes. Dimethylsulfoxide induced a progressive decrease in insulin binding, parallel to the increase in the proportion of differentiated cells. Myeloid cells from CML patients were used to study insulin binding characteristics during spontaneous differentiation. They were separated on Ficoll Hypaque into a light fraction, containing mostly undifferentiated cells, and a dense fraction, containing mostly granulocytes, with similar specific insulin receptor characteristics. Insulin binding capacity, however, was twice as high in the light fraction. To compare binding activity during normal and leukemic myeloid differentiation, cells from normal bone marrow and CML peripheral blood were fractioned by BSA density gradient into enriched fractions of one predominant cell type. Insulin binding decreased in the course of both differentiations. These findings indicate that leukemic immature myeloid cells possess a high number of specific insulin receptors, and that insulin binding decreases during both spontaneous and chemically induced terminal differentiation.
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PMID:Changes in insulin binding activity during myeloid differentiation. 633 51

Tumor cells obtained from leukemia and lymphoma patients were investigated for specific insulin receptors. Using radioactive 125I-labeled insulin, specific insulin binding sites were demonstrated on most acute lymphocytic leukemia (ALL) and acute myelocytic leukemia (AML) cells, including acute promyelocytic leukemia (APL), chronic myelocytic leukemia (CML), and acute monocytic leukemia (AMoL) cells. Insulin receptors were not found on chronic lymphocytic leukemia (CLL) and malignant lymphoma (ML) cells. Specific insulin binding sites were also found on monocytes and thymocytes after treatment with phytohemagglutinin (PHA-P), but not on inactivated tonsil cells, peripheral blood lymphocytes, or thymocytes. There was no inverse correlation between the content of insulin receptors and the basal level of circulating insulin. These data suggest that the insulin receptor may be a new marker of acute leukemia and chronic myelocytic leukemia.
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PMID:Insulin receptors on leukemia and lymphoma cells. 634 73

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

The interleukin-2 receptor (IL-2R) is expressed on proliferating T-lymphocytes following antigen stimulation. Activated IL-2R bearing lymphocytes accumulate as cellular infiltrates in autoimmune thyroiditis, insulin-dependent diabetes mellitus, rheumatoid arthritis and graft rejection. Affected cells in Hodgkin's disease, hairy cell leukaemia, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and lymphoid blast crises of chronic myeloid leukaemia also express IL-2R. Anti-IL-2R monoclonal antibodies or chimeric IL-2R toxins provide a way of selective elimination of such cells. These have been used in experimental models of autoimmunity and transplantation with beneficial results, providing a novel way of selective immunosuppression. In open uncontrolled trials, chimeric IL-2R toxin was found to be safe and effective in patients with refractory rheumatoid arthritis, insulin-dependent diabetes mellitus and IL-2R bearing leukaemias and lymphomas.
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PMID:Immunomodulation by interleukin-2 receptor targeted therapy. 801 99

In patients with chronic myeloid leukemia (CML), the neoplastic (BCR-ABL+) progenitor cells are characterized by an increased proliferative activity. Whether these cells are also resistant to apoptosis and if so, under what conditions remains controversial. We now show that highly purified populations of very primitive neoplastic progenitor cells obtained directly from CML patients survive and proliferate in vitro for several weeks in the absence of any added growth factors (except insulin). In contrast, purified primary normal progenitors maintained under the same conditions die rapidly. Nevertheless, both primary CML cells and BCR-ABL+ BAF3 cells show the same dose-dependent sensitivity to TNF-alpha or ceramide-induced apoptosis as their respective normal counterparts. In fact, time course studies demonstrated an even faster onset of apoptosis in ceramide-treated BCR-ABL+ BAF3 cells as compared to normal controls. BCR-ABL+ cells treated with ceramide also showed a rapid and sequential increase in the tyrosine phosphorylation of p210(BCR-ABL), p46-56SHC and p120Cbl. These findings suggest growth factor deprivation and treatment with TNF-alpha or ceramide trigger different initial events both of which can lead to apoptosis in factor-dependent hematopoietic cells. However, in the first case, activation of apoptosis is blocked by the basal activity of p210(BCR-ABL), whereas in the second, the presence of p210(BCR-ABL) appears to accelerate the onset of apoptosis by a mechanism that may involve an activation of its kinase function.
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PMID:BCR-ABL accelerates C2-ceramide-induced apoptosis. 946 42

Increases in extracellular matrix (ECM) and changes in its components have been documented in the glomeruli of diabetic nephropathy. Advanced glycation end products formed by glycoxidation have been shown to induce the synthesis of ECM components and transforming growth factor beta (TGF-beta), suggesting that advanced glycation end products may be involved in the etiology of imbalance of ECM components in diabetic glomerulosclerosis. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an inbred strain that spontaneously develops non-insulin-dependent diabetes mellitus which progresses to diabetic glomerulosclerosis. Nepsilon-(carboxymethyl)lysine (CML) is known to be formed by glycoxidation. To clarify the involvement of glycoxidation in diabetic nephropathy, we examined the localization of CML, ECM components, and TGF-beta1 in the glomeruli of OLETF rats. The amounts of alpha3(IV) collagen, type VI collagen, and fibronectin were significantly increased in the glomeruli of OLETF rats, whereas the heparan sulfate proteoglycan levels were decreased. After 6 months of age, CML levels were significantly increased in the mesangial area of the glomeruli in these animals. The overexpression of TGF-beta1 preceded the increase in glomerular ECM components. The present study demonstrated that the accumulation of CML precedes the changes of glomerular ECM components in the glomeruli during the course of diabetic nephropathy, suggesting that glycoxidation may be one of the major causes of diabetic glomerulosclerosis.
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PMID:Accumulation of Nsigma-(carboxy-methyl)lysine and changes in glomerular extracellular matrix components in Otsuka Long-Evans Tokushima fatty rat: a model of spontaneous NIDDM. 968 63


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