Lymphoblastic leukaemia cells

The biochemical pharmacology of the MTX analogues (VIII.268)-(VIII.270) has been investigated also by McGuire et al. [380]. In assays using purified DHFR from K562 human myeloblastic leukaemia cells and CCRF-CEM lymphoblastic leukaemia cells, IC50 values of 2-4 nM for... 

DE was used to identify cellular proteins in T and B acute lymphoblastic leukaemia cell lines (Mohammad et al, 1994b). Two B cell and two T cell lines as well as a normal Epstein-Barr virus-transformed line of B cell origin were studied. Despite the great similarities in the patterns of the B and T cell derived from 2-DE gels, three proteins appeared to be unique to B cells, whereas eight proteins were unique to T cell lines. It is not known if these proteins are markers for B or T acute lymphoblastic leukaemia, respectively, or if they are unique to the cell lines that were studied. 

Bacher, N., M. Tiefenthaler, S. Sturm, et al. 2006. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, Go/Gi-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells. Br. J. Haematol. 132(5) 615-622. 

Kumar, K. A., K. M. Arunasree et al. 2009. Effects of (15S)-hydroperoxyeicosatetraenoic acid and (15S)-hydroxyeicosatetraenoic acid on the acute- lymphoblastic-leukaemia cell Une Jurkat Activation of the Fas-mediated death pathway. Biotedmol lBwdwm S2(Pt 2) 121-133. 

L-Asparaginase, an enzyme derived from E. coli or Erwinia carotovora, has been employed in cancer chemotherapy where its selectivity depends upon the essential requirement of some tumours for the amino acid L-asparagine. Normal tissues do not require this amino acid and thus the enzyme is administered with the intention of depleting tumour cells of asparagine by converting it to aspartic acid and ammonia. Whilst L-asparaginase showed promise in a variety of experimentally induced tumours, it is only useful in humans for the treatment of acute lymphoblastic leukaemia, although it is sometimes used for myeloid leukaemia. 

Three cyclic octapeptides, patellamides A-C (21-23) were isolated from L. patella and cytotoxicity data for these compounds and for ulicyclamide (15) and ulithiacyclamide (16) against L1210 murine leukaemia cells and the human acute lymphoblastic leukaemia (ALL) cell line CEM were reported [52]. The structures of the patellamides were later reassigned on the basis of synthetic studies. The proposed structures of patellamides B (22) and C (23) were synthesised and the products were shown to differ from the natural products. This led to new structures being proposed [53,54]. Separate syntheses of... 

Tiley C, Grimwade D, Findlay M, Treleaven J, Height S, Catalano J, Powles R. Tumour lysis following hydrocortisone prior to a blood product transfusion in T-cell acute lymphoblastic leukaemia. Leuk Lymphoma 1992 8(l-2) 143-6. 

Cecchinato V, Chiaramonte R, Nizzardo M, Cristofaro B, Basile A, Sherbet GV, Comi P. 2007. Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells. Biochem Pharmacol 74 1568-1574. 

Up-regulation of annexin 2 has also been implicated in pro-B cell acute lymphoblastic leukaemia ALL (Matsunaga et al., 2004). This occurs as a result of a different translocation t(17 19)(q22 pl3) and the expression of the fusion protein E2A-HLF is also associated with poor prognosis, hypercalcemia and haemorrhagic complications. Expression of E2A-HLF was sufficient to induce annexin 2 overexpression in leukaemic cell lines. 

B25. Brunning, R. D., Borowitz, M. J., Matutes, E., Head, D., Glandrin, G., and Swerdlow, S. H., Precursor B lymphoblastic leukaemia/lymphoblastic lymphoma (precursor B-cell acute lymphoblastic leukaemia). In World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues (E. S. laffe, N. L. Harris, H. Stein, and J. W. Vardiman, eds.), pp. 111-114. IARC Press, Lyon, 2001. 

Another event causing overexpression of transcription factors is juxtaposition of these genes to a gene locus for antigen receptors in T lymphocytes. Nearly half of the genes that are translocated to antigen receptor loci in human leukaemia cells, notably in T-cell acute lymphoblastic leukaemia (T-ALL), encode helix-loop-helix (HLH) transcription factors (such as Max and MAD) (see Chapter 10 and 17). 

Other examples are fusions of the e2a gene, which encodes the E2A transcription factor, a cell-cycle-regulating factor. The e2a gene fuses with genes that encode other transcription factors, such as HLF (hepatocyte leukaemia factor). This causes overexpression of the chimeric transcription factor. Juxtaposition of the trawi-activation domains of E2A and HLE in the E2A-HLF fusion protein results in mismatched heterodimerization and in competition between dimerization partners of E2A-HLF. These gene fusions are the most common changes in the chromosomes of children with acute lymphoblastic leukaemia (ALL). 

CAH Chronic active hepatitis CALLA Common lymphoblastic leukaemia antigen CALX Conjunctival associated lymphoid tissue CaM Calmodulin cAMP Cyclic adenosine monophosphate also known as adenosine 3, 5 -phosphate CAM Cell adhesion molecule CAP57 Cationic protein from neutrophils CAT Catalase CatG Cathepsin G... 

Popat U, Carrum G, Heslop HE. Haemopoietic stem cell transplantation for acute lymphoblastic leukaemia. Cancer Treat Rev 2003 29 3-10. 

Etoposide is administered orally and parenterally in lung cancer (small cells), acute non-lymphoblastic leukaemia and also in Hodgkin s disease, whereas Teniposide is given by intravenous infusion in Hodgkin s disease, and certain forms of cerebral tumours and cancer of the urinary bladder. Etoposide and Teniposide have a cytostatic effect in the S-phase and G2-phase of the life cycle of the cell and differ from other podophyllin derivatives by not causing accumulation in the metaphase but prevent the cell from mitosis or destroy the cells that undergo mitosis. 

Several studies demonstrated that aloin, another natural anthraquinone with potential antitumor activity, was effective on mice bearing solid Erlich carcinoma [29-31], The antitumor activity of aloin was also examined against two epithelial-type tumor cell lines, breast and ovarian [32], Other natural anthraquinones isolated from the roots of Morinda elliptica Ridl. were assayed for their cytotoxic activities. Of these, only damnacanthal was very cytotoxic against the breast carcinoma MCF-7 and T-lymphoblastic leukaemia CEM-SS cell lines [33],... 

---