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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics of insulin receptor binding and structure and its proliferative and metabolic action in a human leukemic cell line was investigated during the cell cycle. Exponentially growing cells were separated by counterflow centrifugation which fractionates cells primarily on the basis of size into subpopulations representing G0/G1, S, and G2 + M cells. This method avoids disturbance of the cellular metabolism. After separation the cells showed a viability of at least 92%, underwent further proliferation, and remained morphologically unchanged, which was shown by electron microscopy. The cells could be enriched to 70-90% purity for G0/G1 phase and 50-60% purity for S and G2 + M phase, respectively, which was shown by DNA flow-cytometry. Specific binding of insulin could be demonstrated in G0/G1, S, and G2 + M enriched cells. Insulin binding sites decreased from 20-25,000 per cell in G0/G1 to 1-2,000 in S and increased to 30-50,000 in G2 + M. The affinity of insulin binding remained nearly constant during the cell cycle. The specificity of the insulin receptor could also be demonstrated by covalent crosslinking of the receptor to radiolabeled ligand in all enriched cell fractions. Glucose transport was stimulated by insulin independently of cell cycle. An increase to 140% of control was observed at an insulin concentration of 10 ng/ml. In contrast, glycogen synthesis could only be stimulated by insulin in the G0/G1 phase. An increase to 140% of control was already reached at 0.25 ng/ml insulin. Insulin in concentrations of 1 and 10 ng/ml stimulated the transit to S-phase in cycling, but not in resting, cells. The growth promoting action of insulin could be investigated by consecutive DNA analysis of the separated cells which had been stimulated by insulin.
Leukemia 1990 Feb
PMID:Role of insulin during cell cycle in a myeloid cell line. 240 14

The immunological phenotypes of leukemia cell samples from 60 patients, of whom 54 had acute myeloid leukemia (AML), were assessed with a panel of monoclonal antibodies (Mabs) with specificity for the following epitopes: Epitopes associated with myeloid leukemia cells, Epitopes expressed only on immature myeloid cells (or subsets) and on monocytes, Epitopes only expressed on granulocytes or on granulocytes and mature myeloid cells (promyelocytes, myelocytes and monocytes), Epitopes on HLA-class II (DR) and HLA-class I molecules and on insulin receptors. This panel of Mabs proved useful to identify leukemia cells in blood and to assess their myeloid origin. The panel of Mabs was found also to be useful for immunophenotyping of leukemia cells. Furthermore, the analysis revealed considerable variations in the immunological phenotype of AML cells, reflecting antigenic heterogeneity within the individual leukemia cell population as well as abnormal or no expression of histocompatibility antigens and insulin receptors in some samples. Some of the Mabs bound preferentially to subgroups in the French-American-British (FAB) classification.
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PMID:Specificity and diagnostic implications of the reactivity pattern of a panel of monoclonal antibodies against myeloid leukemia cells. 243 58

The effect on carbohydrate metabolism of a high dose growth hormone (GH) regimen (1.2 U/kg per week) was assessed on 24 children who had previously been treated for leukaemia. Sixteen patients received high dose GH and eight patients received a conventional dose of GH (0.6 U/kg per week). Oral glucose tolerance tests (OGTT) were performed at baseline and after 3 months of treatment with GH. For the entire group between 0 and 3 months, there was a significant increase in mean (and standard deviation) fasting plasma glucose (0.3 +/- 0.6 mmol/L), fasting insulin level (11 +/- 26 mU/L), and 2 h insulin level (20 +/- 40 mU/L). One patient, who received a conventional dose of GH, developed substantial carbohydrate intolerance. For the entire group, there was no change in response to a carbohydrate load at 3 months as measured by the area under the plasma glucose or insulin curve. There was no significant difference between conventional and high dose groups at 3 months as assessed by these parameters. This study demonstrates that a higher dose of GH may be used in these children in an attempt to improve their final height, without increased risk of carbohydrate intolerance in the short term.
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PMID:Carbohydrate metabolism on high dose growth hormone therapy in children treated for leukaemia. 259 Jan 20

Deletion analysis offers a powerful alternative to linkage and karyotypic approaches for human chromosome mapping. A panel of deletion hybrids has been derived by mutagenizing J1, a hamster cell line that stably retains chromosome 11 as its only human DNA, and selecting for loss of MIC1, a surface antigen encoded by a gene in band 11p13. A unique, self-consistent map was constructed by analyzing the pattern of marker segregation in 22 derivative cells lines; these carry overlapping deletions of 11p13, but selectively retain a segment near the 11p telomere. The map orders 35 breakpoints and 36 genetic markers, including 3 antigens, 2 isozymes, 12 cloned genes, and 19 anonymous DNA probes. The deletions span the entire short arm, dividing it into more than 20 segments and define a set of reagents that can be used to rapidly locate any newly identified marker on 11p, with greatest resolution in the region surrounding MIC1. The approach we demonstrate can be applied to map any mammalian chromosome. To test the gene order, we examined somatic cell hybrids from five patients, whose reciprocal translocations bisect band 11p13; these include two translocations associated with familial aniridia and two with acute T-cell leukemia. In each patient, the markers segregate in telomeric and centromeric groups as predicted by the deletion map. These data locate the aniridia gene (AN2) and a recurrent T-cell leukemia breakpoint (TCL2) in the marker sequence, on opposite sides of MIC1. To provide additional support, we have characterized the dosage of DNA markers in a patient with Beckwith-Wiedemann syndrome and an 11p15-11pter duplication. Our findings suggest the following gene order: TEL - (HRAS1, MER2, CTSD, TH/INS/IGF2, H19, D11S32) - (RRM1, D11S1, D11S25, D11S26) - D11S12 - (HBBC, D11S30) - D11S20 - (PTH, CALC) - (LDHA, SAA, TRPH, D11S18, D11S21) - D11S31 - D11S17 - HBVS1 - (FSHB, D11S16) - AN2 - MIC1 - TCL2 - delta J - CAT - MIC4 - D11S9 - D11S14 - ACP2 - (D11S33, 14L) - CEN. We have used the deletion map to show the distribution on 11p of two centromeric repetitive elements and the low-order interspersed repeat A36Fc. Finally, we provide evidence for an allelic segregation event in the hamster genome that underlies the stability of chromosome 11 in J1. The deletion map provides a basis to position hereditary disease loci on 11p, to distinguish the pattern of recessive mutations in different forms of cancer and, since many of these genes have been mapped in other mammalian species, to study the evolution of a conserved syntenic group.
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PMID:A fine-structure deletion map of human chromosome 11p: analysis of J1 series hybrids. 259 51

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 MT-2, derived from an adult T-cell leukaemia (ATL) cell, the Molt-4F, a human T-cell line, and the Isk, an EB virus-transformed B-cell line, were found to have high-affinity receptors for somatostatin, a cyclic tetradecapeptide that inhibits the release of substances such as growth hormone, TSH, glucagon, insulin, secretin, gastrin and cholecystokinin. The quantity of radioactivity bound varied linearly with the number of cells, and was displaced by non-radioactive somatostatin in a concentration-dependent manner. Specific binding of 125I-somatostatin was time- and temperature-dependent and at 22 degrees reached equilibrium within 120 min. Scatchard analysis demonstrated one class of specific-binding sites on MT-2 cells, Isk cells and Molt-4F cells that had respective densities and dissociation constants of 109 pM and 0.64 nM, 102 pM and 1.1 nM, and 5.8 pM and 0.22 nM.
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PMID:Identification of lymphoid cell lines bearing receptors for somatostatin. 289 85

A 75 year old maturity-onset diabetic developed persistent local allergy to insulin. She had coexistent asymptomatic chronic lymphatic leukaemia. All species of insulin provoked a recurrence of the allergy and attempts at hyposensitization and treatment of the leukaemia produced only marginal benefit. Administration of subcutaneous steroids with insulin relieved the problem, but could not be stopped without relapse. Immunological investigations suggested an immune complex-mediated hypersensitivity reaction to insulin. The later development of immune complex-mediated arthropathy tended to support this suggestion. The lack of histological and immunological evidence of an IgE-mediated reaction suggested that in this case the mechanism of insulin allergy and arthralgia was IgG mediated. We suggest that the chronic leukaemia was implicated in both processes by interfering with homeostatic mechanisms that normally prevent the development of autoallergic disorders.
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PMID:Persistent local insulin allergy in a diabetic with chronic lymphatic leukaemia. 294 4

The expression of hormonal and growth factor receptors in leukemic cell lines might be heterogeneous due to the admixture of different cell cycle phases and the presence of yet unidentified sublines. Therefore, cell cycle-specific separation of Burkitt type ALL cells was performed by counterflow elutriation, and by limited dilution procedure three sublines of this cell line were obtained. Counterflow elutriation enriched to 60-80% purity for G1-, S-, and G2-phase which was shown by DNA flow cytometry. Insulin and insulin-like growth factor I (IGF-I) binding was investigated in the G1, S, and G2 phase. Insulin binding sites decreased from 10 to 15,000 per cell in G1 to 1,000-5,000 in S and increased to 40-50,000 in G2. The affinity of insulin binding remained constant during the cell cycle. IGF-I binding sites increased from 2,000 per cell in G1 to 5,000 in S and 15,000 in G2. The affinity of IGF-I binding decreased from G1 toward S and then remained constant in G2. The three isolated clonal sublines differed in numbers of insulin and IGF-I binding sites/cell without differences in affinity. The fact that IGF-I shows higher affinity binding during G1 than during S and G2 Burkitt type ALL cells suggests that IGF-I might be important for initiation of proliferation. The reduction in insulin binding sites during S-phase may indicate refractoriness of the cell to insulin during DNA replication.
Leukemia 1988 Apr
PMID:Heterogeneity of insulin and insulin-like growth factor I binding in a human Burkitt type ALL cell line during the cell cycle and in three Burkitt type ALL sublines. 296 67

The long interspersed repeated DNA family of rats (LINE or L1Rn family) contains about 40,000 6.7-kilobase (kb) long members (1). LINE members may be currently mobile since their presence or absence causes allelic variation at three single copy loci (2, 3): insulin 1, Moloney leukemia virus integration 2 (Mlvi-2) (4), and immunoglobulin heavy chain (Igh). To characterize target sites for LINE insertion, we compared the DNA sequences of the unoccupied Mlvi-2 target site, its LINE-containing allele, and several other LINE-containing sites. Although not homologous overall, the target sites share three characteristics: First, depending on the site, they are from 68% to 86% (A+T) compared to 58% (A+T) for total rat DNA (5). Depending on the site, a 7- to 15-bp target site sequence becomes duplicated and flanks the inserted LINE member. The second is a version (0 or 1 mismatch) of the hexanucleotide, TACTCA, which is also present in the LINE member, in a highly conserved region located just before the A-rich right end of the LINE member. The third is a stretch of alternating purine/pyrimidine (PQ). The A-rich right ends of different LINE members vary in length and composition, and the sequence of a particularly long one suggests that it contains the A-rich target site from a previous transposition.
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PMID:Target sites for the transposition of rat long interspersed repeated DNA elements (LINEs) are not random. 301 80

Late effects of central nervous system (CNS) prophylaxis with cranial radiation (CR) and intrathecal chemotherapy encompass a broad spectrum of phenomena, ranging from fatal leukoencephalopathy to subclinical dysfunctions. Therefore, we studied 55 asymptomatic children with leukemia or solid tumors by means of visual-evoked potentials (VEP) in order to detect subclinical demyelination of the optic pathway after CNS prophylaxis. Ten of the 11 patients showed increased VEP latency after CR with 1,800 cGy, as compared with previous values. One third of our 34 children treated months to years before the study, with 2,400 cGy CR also showed increased VEP latency which was normal in children treated with intrathecal methotrexate only. Growth hormone secretion was investigated using sequential arginine (ARG) and insulin (INS) tolerance tests in 7 leukemic children treated with 1,800 cGy CR. At diagnosis all patients were responsive to both tests; after CNS prophylaxis, 2 patients were still responsive to ARG and INS, whereas the other 5 were responsive to ARG test only. These results are at variance with our previous experience in a series of 22 children treated with 2,400 cGy CR where 2 patients responded to ARG only and 5 did not respond to either stimulus. These data indicate that, even after a reduction of the CR dose, CNS prophylaxis is still associated with subclinical dysfunctions.
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PMID:Some aspects of neurotoxicity associated with central nervous system prophylaxis in childhood leukemia. 312 37


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