Human chronic myelogenous leukemia

The assay was used to determine NAD pyrophosphorylase activity in extracts prepared from human chronic myelogenous leukemia cells, and in extracts prepared from rat tissues. 

Figure 10.9 (a) Scheme of thei-Motif telomeric DNA-based electrochemical DNA (E-DNA) sensor, (b) E-DNA sensor that detects intracellular SWNTs In extracts of the human chronic myelogenous leukemia K562 cells. (Inset) Calibration curve measured in 1 x KT cell mb cell supernatant (cells were cultured In the absence of SWNTs). Reproduced with permission from [76]. Copyright 2009, American Chemical Society... 

The ( ) enantiomer of usnic acid (isolated from Cladonia convoluta) was moderately cytotoxic to various cancer cell lines, such as murine Lewis lung carcinoma, human chronic myelogenous leukemia, human brain metastasis of a prostate carcinoma, human breast adenocarcinoma, and human glioblastoma (Molnar and Farkas 2010 Bezivin et al. 2004). Usnic acid also decreased... 

The so called VIM-2 ganglioside 84 (Scheme 23) is a natural sphingoglycolipid which is regarded as a tumor associated carbohydrate antigen. It has been isolated from human chronic myelogenous leukemia cells. 

Aoki, S., Kong, D., Matsui, K, Rachmat, R., and Kobayashi, M. (2004b) Sesquiterpene anfhraquinones, from a marine sponge, induce erythroid differentiation in human chronic myelogenous leukemia, K562 cells. Chem. Pharm. Butt., 52, 935-937. 

Yuo, A., Kitagawa, S., Okabe, T., Urabe, A., Komatsu, Y., Itoh, S., Takaku, F. (1987). Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia. Blood 70,404-11. 

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinases inhibitor approved for use in patients with chronic myelogenous leukemia after ima-tinib treatment and for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Maximum plasma concentrations (Cmax) of dasatinib are observed between 0.5 and 6 hours (Tmax) following oral administration. Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. CYP3A4 was the primary enzyme responsible for the formation of the active metabolite. The overall mean terminal half-life of dasatinib is 3-5 hours. Adverse events included mild to moderate diarrhea, peripheral edema, and headache. Neutropenia and myelosuppression were common toxic effects. 

Like many other nonreceptor tyrosine kinases, Abl tyrosine kinase may be converted by mutations into a dominant oncoprotein and thus contribute to tumor formation. Abl tyrosine kinase was first discovered as the oncogene of murine Abelson leukemia virus. Chronic myelogenic leukemia in humans is cause by a chromosome translocation in which a fusion protein is created of Abl tyrosine kinase and a Bcr protein (c Chapter 14). The result is a greatly increased tyrosine kinase activity, to which a causal role in occurrence of this leukemia is attributed. 

Uehara, Y., Casa, S., Makita, A., Sakurada, K., and Miyazaki, T., Lysosomal arylsulfatases of human leukocytes Increment of phosphorylated B variant in chronic myelogenous leukemia. Cancer Res. 43, 5618-5622 (1983). 

The third observation that supported a central role for DNA in cancer came from the study of chromosomes in human leukemia cells. Karyotyping is a cytological technique used to characterize the gross structure of chromosomes in mitotic cells. Researchers noticed that in cells from one type of leukemia, chronic myelogenous leukemia, there was almost always a chromosome rearrangement between chromosomes 9 and 22. This reciprocal translocation led to identification of a small 22 9 chromosome which came to be called the Philadelphia chromosome because it was discovered at the Wistar Institute in Philadelphia. Importantly, the karyotype of nonleukemic cells from patients with this form of leukemia is normal. 

---