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 aim of this work is to evaluate the relationship between P-glycoprotein expression in circulating blasts and clinical response in patients suffering from acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, and chronic myeloid leukemia in either lymphoid or myeloid blastic crisis. The results obtained show that: a) patients whose blasts express P-glycoprotein are resistant towards protocols including Doxorubicin, Daunorubicin, Etoposide, Mithramycin, Vincristine; b) P-glycoprotein can be expressed constitutively in some cases; c) P-glycoprotein does not appear to be the only mechanism responsible for resistance towards anthracyclines and Etoposide.
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PMID:P-glycoprotein and drug resistance in acute leukemias and in the blastic crisis of chronic myeloid leukemia. 198 99

Mithramycin induces a reversible inhibition of cellular RNA synthesis without affecting DNA synthesis. The authors have shown this drug induces myeloid differentiation of HL-60 promyelocytic leukemia cells and is an effective agent in certain patients with chronic granulocytic leukemia. In order to investigate the mechanism by which this drug inhibits RNA synthesis we have compared the effect of mithramycin on RNA synthesis by whole cells, isolated nuclei, and RNA synthesis by isolated E. coli RNA polymerase and eukaryotic RNA polymerase II. Exposure of HL-60 cells to mithramycin at concentrations of 4.6 X 10(-7) m or higher for 48 hours causes an almost immediate inhibition of RNA synthesis (up to 85% at 4 hours) with only modest cytotoxicity at these concentrations. Endogenous RNA synthesis by isolated nuclei can be inhibited by mithramycin only at high concentrations (greater than 10(-5) m), suggesting that mithramycin primarily may inhibit initiation, rather than elongation. Mithramycin inhibits in vitro transcription of salmon sperm DNA by E. coli RNA polymerase at DNA:drug ratios similar to those required for RNA synthesis inhibition in whole cells. Similar DNA binding studies with synthetic oligonucleotides demonstrate that mithramycin is a potent inhibitor of transcription of Poly dG.dC by E. coli RNA polymerase but has no effect on transcription of Poly dA.dT. The rapid inhibition of whole cell and isolated RNA polymerase transcription, and the relative insensitivity of isolated nuclei, suggest mithramycin may interact with specific DNA sequences in order to inhibit the initiation of RNA synthesis in intact cells.
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PMID:Mithramycin selectively inhibits transcription of G-C containing DNA. 296 90

A patient with chronic granulocytic leukemia in acute blastic transformation was treated with mithramycin, an RNA synthesis inhibitor, after in vitro exposure of her leukemic cells to mithramycin showed differentiation to normal appearing granulocytes. Mithramycin therapy in vivo resulted in a prompt and dramatic hematologic response. Before therapy, the patient's leukemic cells had high levels of transcription of the cellular myc and abl protooncogenes. After initiation of therapy, protooncogene mRNA decreased rapidly. These observations indicate that mithramycin can induce differentiation both in vitro and in vivo and suggest that such changes may be associated with altered oncogene expression.
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PMID:In vivo differentiation of blast-phase chronic granulocytic leukemia. Expression of c-myc and c-abl protooncogenes. 316 Jul 29

Within a recent one-year period, 3 patients in the accelerated phase of chronic myelogenous leukemia were admitted to our medical center with severe hypercalcemia. Simultaneous determinations of ionized calcium and parathyroid hormone levels in 2 of the patients confirmed the hypercalcemia and revealed suppression of parathyroid hormone. We conclude that hypercalcemia in the accelerated phase of chronic myelogeneous leukemia may be more common than previously described and is not mediated by parathyroid hormone. An elevated parathyroid hormone level accompanying hypercalcemia in these patients should suggest the additional diagnosis of primary hyperparathyroidism. Mithramycin was necessary for control in 2 of our cases as well as in others reported in the medical literature and should be an early therapeutic consideration whenever saline diuresis is inadequate.
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PMID:Hypercalcemia in the accelerated phase of chronic myelogenous leukemia. 645 95

Thirteen patients with accelerated phase of chronic myeloid leukemia (CML-AC) were treated with intravenous plicamycin and subcutaneous alpha-interferon. Two patients stabilized, three patients had partial hematologic responses and one patient had a hematologic complete response with a major cytogenetic response. Two patients, progressing on hydroxyurea, did not respond, but demonstrated re-sensitization to hydroxyurea after completion of induction therapy and had prolonged return to chronic phase for 30 months and 25 months. Four non-responders subsequently received additional chemotherapy and responded. Median survival of all study patients from the development of accelerated phase of CML was 24 months: substantially longer than other reported series (median 6 months). Plicamycin appears to add efficacy to interferon in the stabilization of accelerated phase of CML.
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PMID:A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia. 922 62