Chronic myelogenic leukemia

The plasma half-life of 6-MP after intravenous bolus injection is 21 min in children and is twofold greater in adults. After oral intake peak levels are attained within 2 h. 6-MP is used for the treatment of ALL and has shown certain activity in chronic myelogenous leukemia. The major side effects involve myelosuppression, nausea, vomiting, and hepatic injury. 

In chronic myelogenous leukemia (CML) as well as in a subset of acute lymphoblastic leukemia (ALL) Bcr-Abl, a fusion protein of c-Abl and the breakpoint cluster region (bcr), is expressed in the cytosol of leukemic cells. This fusion protein forms homo-oligomeric complexes that display elevated kinase activity and is the causative molecular abnormality in CML and certain ALL. The transforming effect of Bcr-Abl is mediated by numerous downstream signaling pathways, including protein kinase C (PKC), Ras-Raf-ERK MAPK, JAK-STAT (see below), and PI3-kinase pathways. 

Acute lymphatic leukemia, acute or chronic myelogenous leukemia... 

A detailed study of the 0-linked oligosaccharides present on the surface of normal granulocytes, chronic myelogenous leukemia cells, and acute myelogenous leukemia cells has been completed. Structures were elucidated by f.a.b.-m.s. after permethylation, and methylation analysis before and after specific exo-glycosidase treatments. Some of the components were shown by f.a.b.-m.s. to be poly(N-acetyllactosaminyl) oligosaccharides, for example, 29. 

Mercaptopurine (6-MP) is an oral purine analog that is converted to a ribonucleotide to inhibit purine synthesis. Mercaptopurine is converted into thiopurine nucleotides, which are catabolized by thiopurine S-methyltransferase (TPMT), which is subject to genetic polymorphisms and may cause severe myelosuppression. TPMT status may be assessed prior to therapy to reduce drug-induced morbidity and the costs of hospitalizations for neutropenic events. Mercaptopurine is poorly absorbed, with a time to peak concentration of 1 to 2 hours after an oral dose. The half-life is 21 minutes in pediatric patients and 47 minutes in adults. Mercaptopurine is used in the treatment of acute lymphocytic leukemia and chronic myelogenous leukemia. Significant side effects include myelosuppression, mild nausea, skin rash, and cholestasis. When allopurinol is used in combination with 6-MP, the dose of 6-MP must be reduced by 66% to 75% of the usual dose because allopurinol blocks the metabolism of 6-MP. 

Idarubicin inhibits both DNA and RNA polymerase, as well as topoisomerase II. The pharmacokinetics of idarubicin can best be described by a three-compartment model, with an a half-life of 13 minutes, a (3 half-life of 2.4 hours, and a terminal half-life of 16 hours.22 Idarubicin is metabolized to an active metabolite, idarubicinol, which has a half-life of 41 to 69 hours. Idarubicin and idarubicinol are eliminated by the liver and through the bile. Idarubicin has shown clinical activity in the treatment of acute leukemias, chronic myelogenous leukemia, and myelodysplastic syndromes. Idarubicin causes cardiomyopathy at cumulative doses of greater than 150 mg/m2 and produces cumulative cardiotoxic effects with other anthracyclines. Idarubicin is a vesicant and causes red-orange urine, mucositis, mild to moderate nausea and vomiting, and bone marrow suppression. 

Explain the role of the Philadelphia chromosome in the pathophysiology of chronic myelogenous leukemia (CML). 

Chronic leukemia consists of a number of disorders, including chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL). 

CML Chronic myelogenous leukemia EBV Epstein-Barr virus... 

Chen J, Zhang J, Fluang L et al (2008) Flybridization biosensor using 2-nitroacridone as electrochemical indicator for detection of short DNA species of Chronic Myelogenous Leukemia. Biosens Bioelectron 24 349-355... 

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