Myelocytic leukemia

Hydroxyurea is an oral drug that inhibits ribonucleotide reductase, which converts ribonucleotides into the deoxyribuon-cleotides used in DNA synthesis and repair. The time to peak concentrations of hydroxyurea is 1 to 2 hours after oral administration. Approximately 50% is degraded by the liver to form urea and respiratory carbon dioxide. The remainder is excreted by the kidney. The half-life ranges from 3.5 to 4.5 hours. Hydroxyurea has shown clinical activity in the treatment of chronic myelocytic leukemia, polycythemia vera, and thrombocytosis. The major side effects are myelo-suppression, nausea and vomiting, diarrhea, and constipation. Rash, mucositis, and renal tubular dysfunction occur rarely. 

As well as NONOates, other NO donors also showed anticancer activity independently. Sodium nitroprusside (SNP), a metal-NO complex, showed cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma [109]. SNP and cytosine arabinoside (Ara-C) did not share the drug resistance. Interestingly, SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP has an anti-tumor effect on human hematological malignant cells. 

Kinases Abl kinase Mouse cDNA Cancer, acute lymphocytic leukemia, chronic myelocytic leukemia, chronic neutrophilic leukemia Regulation of cytoskeletal organization and movement... 

Imatinib caused a revolution in the treatment of chronic myelocytic leukemia... 

Numerous case reports and epidemiological studies suggest a leukemogenic action of benzene in humans—the leukemia tending to be acute and myeloblastic in type, often following aplastic changes in the bone marrow. Acute myelocytic leukemia may be preceded by myelodysplastic syndrome, a preleukemic state characterized by abnormal marrow architecture, inadequate hematopoiesis, and many cells with chromosome damage." Benzene may also induce chronic types of leukemia. ... 

II. Israels, L. G., Delory, G. E., Hnatiuk, L., and Friesen, E., Studies on the etiology of the elevated serum isomerase in chronic myelocytic leukemia. Blood 13, 78-84 (1958). 

An oxime derivative of indirubin (a natural bis-indole alkaloid used in traditional Chinese medicine to treat chronic myelocytic leukemia), indirubin-3 -monoxime (37), was found to be a potent inhibitor of cyclin-dependent kinases (CDKs), and of the proliferation of myeloid leukemia cells via inhibition of a tyrosine kinase . The 3D structure of the complex of 37 with CDK revealed that the oxime function is intact, and that it occupies the ATP-ribose site of the CDK-ATP structure. While the specific role of the oxime group in the biological activity of 37 is not clear, it was proposed that its reactivity may be utilized for further drug design... 

Although 6-thioguanine is chiefly used in chemotherapy for acute myelocytic leukemia and other marrow-based malignancies, lower doses are very effective for moderate to severe psoriasis, particularly in... 

Patients with other types of unresectable cancer also may benefit from chemotherapy, as evidenced by prolongation of life, shrinkage of tumor, and improvement in symptoms. Notable among these are ovarian epithelial and breast carcinomas, oat cell (small cell undifferentiated) carcinoma of the lung, and acute myelocytic leukemia. Cancers that are for the most part resistant to today s agents include melanoma, colorectal and renal carcinomas, and non-oat cell cancers of the lung. 

Chronic myelocytic leukemia (CML) Interferon alfa-2a-. Subcutaneous, IM 9 million units daily. 

Treatment of bladder, cervical, renal carcinoma, chronic myelocytic leukemia, laryngeal papillomatosis, multiple myeloma, mycosis fungoides... 

Uniabeied Uses Treatment of acute myelocytic leukemia bladder, cervical, ovarian, prostatic, renal, and testicular carcinomas psoriatic arthritis systemic dermatomyo-sitis... 

Rozemuller, H., W.I Rombouts, IP. Touw, D.I FitzGerald, R.I Kreitman, I. Pastan, A. Hagenbeek, and A.C. Martens, Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model. Leukemia, 1996.10(11) 1796-803. 

Lee, L.S. Cheng, Y.C. Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. J. Biol. Chem., 252, 5686-5691 (1977)... 

Colchicine is a poisonous tricyclic tropane alkaloid from the autumn crocus (Colchicum autumnale) and gloriosa lily (Gloriosa superba). This alkaloid is a potent spindle fiber poison, preventing tubulin polymerization.25 Colchicine has been used as an effective anti-inflammatory drug in the treatment of gout and chronic myelocytic leukemia, but therapeutic effects are attainable at toxic or near toxic dosages. For this reason, colchicine and its analogs are primarily used as biochemical tools in the mechanistic study of new mitotic inhibitors. 

Busulfan Myleran Chronic myelocytic leukemia Blood disorders (anemia, leukopenia, thrombocytopenia] metabolic disorders (hyperuricemia, fatigue, weight loss, other symptoms]... 

Cyclophosphamide Cytoxan, Neosar Acute and chronic lymphocytic leukemia acute and chronic myelocytic leukemia carcinoma of ovary, breast Hodgkin disease non-Hodgkin lymphomas multiple myeloma Blood disorders (anemia, leukopenia, thrombocytopenia] Gl distress (nausea, vomiting, loss of appetite] bladder irritation hair loss car-diotoxicity pulmonary toxicity... 

Idarubicin Idamycin Acute myelocytic leukemia Similar to daunorubicin... 

Drug(s) Biologic response modifiers Interferons Interferon alfa-2a [Roferon-A] Interferon alfa-2b [Intron-A] Primary Antineoplastic Indication(s) Hairy-cell leukemia Kaposi sarcoma chronic myelocytic leukemia renal and bladder cancers Common Adverse Effects Flulike syndrome [mild fever, chills, malaise]... 

The alkyl sulfonate busulfan (Myleran) is metabolized to an alkylating agent. Because it produces selective myelosuppression, it is used in cases of chronic myelocytic leukemia. It causes pronounced hyperuricemia stemming from the catabolism of purine. 

Apart from DNA methylation studies, the second aspect of epigenetic misregulation involves disruption of histone acetylation and chromatin structure. Functional disruption of some HATs genes (such as the CBP and p300) is detected in some cancers, most notably, acute pro-myelocytic leukemia (51). This has lead to the hope that HD AC inhibitors will be useful for the treatment of this disease and a number of inhibitors are currently being assessed in clinical trials (see below). 

Harringtonine appears to be the most effective agent and recent studies in the People s Republic of China have shown that it is effective against L615 leukemia, L7212 leukemia, sarcoma 180, and Walker carcinosarcoma 256 (188). Harringtonine also appeared to be effective in the treatment of acute and chronic myelocytic leukemia in humans (189). 

Therapeutic applications Applications for these two agents differ despite their structural similarity and their apparently similar mechanisms of action. Doxorubicin is one of the most important and widely used anticancer drugs. It is used for treatment of sarcomas and a variety of carcinomas, including breast and lung, as well as acute lymphocytic leukemia and lymphomas. Daunorubicin is used in the treatment of acute lymphocytic and myelocytic leukemias. 

Bhaskar, N., Hosokawa, M., and Miyashita, K. 2004c. Growth inhibition of human pro-myelocytic leukemia (9HL-60) cells by lipid extracts of marine alga Sargassam marginatum (fucales, Phaeophyta) harvested off Goa (west coast of India) with special reference to fatty acid composition. Indian J. Marine Sci., 33, 355-360. 

Defective nitrovasodilator-stimulated protein phosphorylation and calcium regulation in cGM P-dependent protein kinase-defident human platelets of chronic myelocytic leukemia. Biol. 

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