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

The present study was undertaken to investigate the potential role of glucocorticoid-induced DNA damage in the lysis of human lymphoid leukemia cells by glucocorticoids. Lymphoblasts were isolated from patients with acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia (CML) in blast crisis and cultured in vitro with or without dexamethasone. DNA was then purified from the cells and analyzed by agarose gel electrophoresis. Only high molecular weight (mol wt) DNA was present in cells cultured without dexamethasone, but a ladder of DNA fragments ranging in size from 180 to 200 base pairs (bp) to greater than 1,500 bp was present in cells cultured with dexamethasone. The DNA fragments were multiples of 180 to 200 bp, suggesting an internucleosomal site of DNA cleavage. The same pattern of DNA fragmentation was detected in normal thymocytes isolated from adrenalectomized rats following in vivo treatment with dexamethasone and in S49 mouse thymoma cells after in vitro incubation with dexamethasone. Dexamethasone-induced DNA fragmentation preceded overt loss of viability in glucocorticoid-sensitive cells but was not detected in two variants of the S49 cell line that are glucocorticoid resistant owing to glucocorticoid receptor defects. The results suggest that glucocorticoids kill human lymphoblastic leukemia cells and both normal and malignant murine thymocytes by a common mechanism that involves glucocorticoid induction of an endonucleolytic activity with cleavage of genomic DNA.
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PMID:Glucocorticosteroids induce DNA fragmentation in human lymphoid leukemia cells. 326 87

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

We have investigated glucocorticoid receptor (GR) level, terminal deoxynucleotidyl transferase (TdT) activity and the initial responsiveness to prednisone and vincristine in 31 patients with acute lymphatic leukemia (ALL) and with chronic myelogenous leukemia in blast transformation (CML/BT). All 11 patients with low levels of GR (5,000 binding sites per cell) were resistant to this initial treatment whereas 13 of the 20 patients with high levels of GR responded readily. The correlations between clinical responsiveness and TdT activity were significant to the p less than 0.005 level but there was no linear correlation (r = 0.3427) between GR-level and TdT activity. High levels of both GR and TdT seemed to be associated with better prognosis in patients with these leukemias. Thus the determination of GR and TdT might help selection of patients likely to respond to prednisone and vincristine in ALL and CML/BT.
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PMID:Glucocorticoid receptor level, terminal deoxynucleotidyl transferase activity and initial responsiveness to prednisone and vincristine in leukemia. 657 18

In an attempt to investigate the utility of glucocorticoid receptor determination to predict clinical responsiveness in human leukemias we have studied glucocorticoid receptors in the leukemic cells from 46 patients and in the lymphocytes from 18 normal donors. In the normal lymphocytes there were 3,875 (Median) specific binding sites per cell. The blasts from 17 patients with ANLL had on average higher levels of binding sites per cell (Median = 7,250, range: 0 to 15,295) than the other leukemias. Of the 15 patients with CLL, six had received glucocorticoid treatment for 3 to 5 years. Their lymphocytes had lower number of receptors (Median = 2,000) than the other cases which were newly diagnosed (Median = 4,500). Four patients had ALL/AUL, three patients had blast crisis as terminal phase of CML, and seven had leukemic Non-Hodgkin lymphomas (Median = 3,500 sites/cell). In 24 patients we have also studied the in vitro sensitivity of the leukemic cells to dexamethasone. There was no marked correlation between glucocorticoid receptor levels and in vitro sensitivity. An attempt to correlate receptor levels with clinical responsiveness demonstrated that glucocorticoid receptor determination might be of value in patients with lymphoid malignancies but probably not in patients with other leukemias.
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PMID:Glucocorticoid receptors and sensitivity in leukemias. 693 62

The glucocorticoid receptor (GR) quantitation by a whole-cell assay and/or cytosol technique and the in vitro sensitivity to steroids have been assessed in peripheral blood cells from normal donors and patients with chronic lymphatic leukemia (CLL), acute lymphoblastic leukemia (ALL), lymphosarcoma cell leukemia (LSCL), acute nonlymphatic leukemia (ANLL), and chronic myeloid leukemia (CML). Within the lymphoproliferative diseases, ALL cells exhibited the highest GR concentration (regardless of the method used) and the highest in vitro inhibition of spontaneous [3H]thymidine ([3H]TdR) uptake by glucocorticoids. A significant relationship between GR concentration (whole-cell assay) and in vitro sensitivity to dexamethasone was also found. On the contrary, CLL cells presented the highest sensitivity to glucocorticoids in PHA-stimulated cell cultures. Cells from the only two ALL patients who did not undergo a remission after glucocorticoid-inclusive chemotherapy had both the lowest in vitro sensitivity to dexamethasone and the lowest GR concentration with whole-cell assay. Concerning myeloid leukemia, ANLL patients had GR concentrations slightly higher than those found in the ALL group but exhibited the lowest degree of inhibition of spontaneous [3H]TdR uptake by dexamethasone (stimulatory effects occurred in some cases). CML cells exhibited an inhibition degree by in vitro glucocorticoids significantly higher than that of ANLL cells but not different from that of lymphoproliferative diseases. No clear relationship among GR pattern, in vitro cell sensitivity to glucocorticoids, and clinicohematologic parameters was observed in myeloid leukemia-bearing patients.
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PMID:Glucocorticoid receptor and in vitro sensitivity to steroid hormones in human lymphoproliferative diseases and myeloid leukemia. 694