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Human Leukemia (human + leukemia)
Terms modified by Human Leukemia Selected AbstractsRedundant role for Zap70 in B cell development and activationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Farnaz Fallah-Arani Dr. Abstract Expression of the Syk family tyrosine kinase Zap70 is strongly correlated with poor clinical outcome in chronic lymphocytic leukemia, the most common human leukemia characterized by B cell accumulation. The expression of Zap70 may reflect the specific cell of origin of the tumor or may contribute to pathology. Thus, the normal role of Zap70 in B cell physiology is of great interest. While initial studies reported that Zap70 expression in the mouse was limited to T and NK cells, more recent work has shown expression in early B cell progenitors and in splenic B cells, suggesting that the kinase may play a role in the development or activation of B cells. In this study, we show that Zap70 is expressed in all developing subsets of B cells as well as in recirculating B cells, marginal zone B cells and peritoneal B1 cells. Analysis of Zap70-deficient mice shows no unique role for Zap70 in either the development of B cells or in their in vitro and in vivo activation. However, we show that Zap70 can rescue the defective positive selection of immature B cells into the recirculating pool in Syk-deficient mice, demonstrating functional redundancy between these two kinases. [source] Mixed lineage leukemia histone methylases play critical roles in estrogen-mediated regulation of HOXC13FEBS JOURNAL, Issue 24 2009Khairul I. Ansari HOXC13, a homeobox-containing gene, is involved in hair development and human leukemia. The regulatory mechanism that drives HOXC13 expression is mostly unknown. Our studies have demonstrated that HOXC13 is transcriptionally activated by the steroid hormone estrogen (17,-estradiol; E2). The HOXC13 promoter contains several estrogen-response elements (EREs), including ERE1 and ERE2, which are close to the transcription start site, and are associated with E2-mediated activation of HOXC13. Knockdown of the estrogen receptors (ERs) ER, and ER, suppressed E2-mediated activation of HOXC13. Similarly, knockdown of mixed lineage leukemia histone methylase (MLL)3 suppressed E2-induced activation of HOXC13. MLLs (MLL1,MLL4) were bound to the HOXC13 promoter in an E2-dependent manner. Knockdown of either ER, or ER, affected the E2-dependent binding of MLLs (MLL1,MLL4) into HOXC13 EREs, suggesting critical roles of ERs in recruiting MLLs in the HOXC13 promoter. Overall, our studies have demonstrated that HOXC13 is transcriptionally regulated by E2 and MLLs, which, in coordination with ER, and ER,, play critical roles in this process. Although MLLs are known to regulate HOX genes, the roles of MLLs in hormone-mediated regulation of HOX genes are unknown. Herein, we have demonstrated that MLLs are critical players in E2-dependent regulation of the HOX gene. [source] Pyrrolizidine Alkaloids and Bisabolane Sesquiterpenes from the Roots of Ligularia cymbuliferaHELVETICA CHIMICA ACTA, Issue 2 2008Chun-Mei Liu Abstract The new pyrrolizidine alkaloid glycoside 1, and the three new highly oxygenated bisabolane sesquiterpenes 4,6, together with the two known pyrrolizidine alkaloids 2 and 3, were isolated from the roots of Ligularia cymbulifera (W.,W. Smith) Hand.- Mazz. Their structures were established on the basis of spectroscopic analysis, especially 1D- and 2D-NMR data. The cytotoxic activities of compounds 1, 2, and 4,6 were evaluated against hepatoma (BEL-7402), human leukemia (HL-60), human ovarian carcinoma (HO-8910), and nasopharyngeal carcinoma (KB) cell lines (Tables 1,3). Compound 6 showed weak cell-growth inhibition of BEL-7402 cell. [source] ETS transcription factors: Possible targets for cancer therapyCANCER SCIENCE, Issue 8 2004Tsuneyuki Oikawa Ets family (ETS) transcription factors, characterized by an evolutionally conserved Ets domain, play important roles in cell development, cell differentiation, cell proliferation, apoptosis and tissue remodeling. Most of them are downstream nuclear targets of Ras-MAP kinase signaling, and the deregulation of ETS genes results in the malignant transformation of cells. Several ETS genes are rearranged in human leukemia and Ewing tumors to produce chimeric oncoproteins. Furthermore, the aberrant expression of several ETS genes is often observed in various types of human malignant tumors. Considering that some ETS transcription factors are involved in malignant transformation and tumor progression, including invasion, metastasis and neo-angiogenesis through the activation of cancer-related genes, they could be potential molecular targets for selective cancer therapy. [source] Role of AML1/Runx1 in the pathogenesis of hematological malignanciesCANCER SCIENCE, Issue 10 2003Mineo Kurokawa AML1/Runx1, originally identified as a gene located at the breakpoint of the t(8;21) translocation, encodes one of the two subunits forming a heterodimeric transcription factor. AML1 contains a highly evolutionally conserved domain called the Runt domain, responsible for both DNA binding and heterodimerization with the partner protein, CBF,. AML1 is widely expressed in all hematopoietic lineages, and regulates the expression of a variety of hematopoietic genes. Numerous studies have shown that AML is a critical regulator of hematopoietic development. In addition, AML1 and CBF, are frequent targets for chromosomal translocation in human leukemia. Translocations lead to the generation of fusion proteins, which play a causative role for the development of leukemia, primarily by inhibiting AML1 function. Point mutations that impair AML1 function are also associated with familial and sporadic leukemias. Loss of AML1 function is thus implicated in a number of leukemias through multiple pathogenic mechanisms. However, AML1-related translocations or haploinsufficiency of AML1 are not immediately leukemogenic in animal models, suggesting that additional genetic events are required for the development of full-blown leukemia. [source] Cepharanthine activates caspases and induces apoptosis in Jurkat and K562 human leukemia cell linesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2001Jianghong Wu Abstract Cepharanthine (CEP) is a known membrane stabilizer that has been widely used in Japan for the treatment of several disorders such as anticancer therapy-provoked leukopenia. We here report that apoptosis was induced by low concentrations (1,5 ,M) of CEP in a human leukemia T cell line, Jurkat, and by slightly higher concentrations (5,10 ,M) in a human chronic myelogenous leukemia (CML) cell line K562, which expresses a p210 antiapoptotic Bcr-Abl fusion protein. Induction of apoptosis was confirmed in both Jurkat and K562 cells by DNA fragmentation and typical apoptotic nuclear change, which were preceded by disruption of mitochondrial membrane potential and were induced through a Fas-independent pathway. CEP treatment induced activation of caspase-9 and -3 accompanied by cleavage of PARP, Bid, lamin B1, and DFF45/ICAD in both Jurkat and K562 cells, whereas caspase-8 activation and Akt cleavage were observed only in Jurkat cells. The CEP-induced apoptosis was completely blocked by zVAD-fmk, a broad caspase inhibitor. Interestingly, CEP treatment induced remarkable degradation of the Bcr-Abl protein in K562 cells, and this degradation was prevented partially by zVAD-fmk. When used in combination with a nontoxic concentration of herbimycin A, lower concentrations (2,5 ,M) of CEP induced obvious apoptosis in K562 cells with rapid degradation or decrease in the amount of Bcr-Abl and Akt proteins. Our results suggest that CEP, which does not have bone marrow toxicity, may possess therapeutic potential against human leukemias, including CML, which is resistant to anticancer drugs and radiotherapy. J. Cell. Biochem. 82: 200,214, 2001. © 2001 Wiley-Liss, Inc. [source] Assignment of the Raman-active modes of the antitumor agent azathioprine by normal-mode calculationsJOURNAL OF RAMAN SPECTROSCOPY, Issue 10 2001Alberto Vivoni Azathioprine is a slow-release prodrug of 6-mercaptopurine and an established clinical agent for the treatment of human leukemias and other immunologically mediated diseases. The Raman spectra (1600,600 cm,1) of solid and solution azathiopurine were recorded and are presented along with results from normal-mode calculations. The band assignments were derived from semi-empirical and ab initio molecular orbital calculations. The ab initio calculations were performed with the restricted Hartree,Fock method and the semi-empirical methods utilized the AM1, PM3 and MNDO-d methods. Copyright © 2001 John Wiley & Sons, Ltd. [source] | |||||||||||||