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 present AML protocol which only applies one anthracycline associated with arabinosyl-cytosine gives a first remission plateau of 65% and a 75% survival plateau at five years. Contrary to other teams, we do not apply the allogenic bone marrow graft at the first remission but at the second one. The new protocol comprises application of two anthracyclines, adriamycin and aclacinomycin, a possible autologous bone marrow graft at first remission upon reinforcement, a combination of methotrexate and thioguanine as maintenance chemotherapy and immunotherapy with bestatine. The two protocols respectively applied to the ALL good prognosis and reserved prognosis, give 85% global survival. The autologous bone marrow graft is added at first remission to B or T forms or voluminous CALLA + types. The advantage of CNS radiotherapy is compared with its disadvantages. Bestatine is employed in immunotherapy. The immunoprevention protocol applied to CML blastic crisis (vaccination with a pool of CB blasts) from the second year has prolonged survival of patients suffering from this affection and also treated by splenectomy and hydroxyurea. Allogeneic or autologous bone marrow graft is added to the protocol. The same protocol is applied to not very aggressive LLC and LNH (lymphocytic and centrofollicular with small cleaved nucleus cells) and includes maximum remission induced by chemotherapy followed by immunotherapy (by thymuline and then, if immunity disorders are not corrected, by zinc, then bestatine and finally tuftsin). A similar sequence was applied to the myeloma, comprising MLP-PDN-CPM chemotherapy to induce remission, combination of MLP-PDN and CPM and, if there is resistance, CLB, 6-TG, PDN and TNP. Interferon is appropriate with certain cytopenic forms. A protocol comprising VCR, ADM, PDN, CPM and TNP is applied to centrofollicular NHL with small non cleaved nucleus cells or large cells. As Hoerni and Jones have obtained significant benefits with BCG, its terminal application is compared with that of bestatine. Finally a less mutagenic protocol than MOPP and/or ABVD is proposed for Hodgkin's disease. In this protocol, two cycles alternate, and they combine: a) firstly VCR, PDN, THP-ADM and VPS, and b) secondly VLB, DXM, ACM and TNP with alternatively BLM and PPM between the cycles. This chemotherapy is followed by the same immunorestoration protocol as that applied to LLC and myeloma.
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PMID:[Protocols for the treatment of leukemia and lymphoma: toward escalation or toward reduction of degree?]. 638 Jun 5