Myeloid leukaemia

Rapozzi V., Burm B.E.A., CoGOi S., Van DER Marel G.A., Van Boom J.H., Quad-RiFOGLio F., XoDO L. E. Antiproliferative effect in chronic myeloid leukaemia cells by antisense peptide nucleic acids. Nucleic Acids Res. 2002 30 3712-3721. 

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. 

CLC Charcot-Leyden crystal CMC Critical micellar concentration CMI Cell mediated immunity CML Chronic myeloid leukaemia CMV Cytomegalovirus CNS Central nervous system CO Cyclooxygenase CoA Coenzyme A CoA-IT Coenzyme A - independent transacylase... 

Ajoene has antitumor activity, inhibits cholesterol biosynthesis, modulates membrane-dependent functions of immune cells, inhibits protein prenylation83 and is an anti-leukaemia agent for acute myeloid leukaemia.85 In antithrombotic assays, the Z isomer is more active than the E isomer.84... 

Further studies have shown additional cancer types, most notably ovarian and bladder cancer, non-Hodgkin s lymphoma and acute myeloid leukaemia, to be at least partially responsive to IL-2 treatment. However, a persistent feature of clinical investigations assessing IL-2 effects on various cancer types is variability of response. Several trials have yielded conflicting results, and no reliable predictor of clinical response is available. 

The G-CSF receptor has been well characterized. It is a single transmembrane polypeptide found on the surface of neutrophils, as well as in various haemopoietic precursor cells, platelets, endothelial cells and, notably, various myeloid leukaemias. (Myeloid means derived from bone marrow leukaemia refers to a cancerous condition in which there is uncontrolled overproduction of white blood cells in the bone marrow or other blood-forming organs. The white cells produced are generally immature/abnormal and result in the suppression of production of healthy white blood cells.)... 

G-CSF receptors are also found on human myeloid leukaemia cells, leu-kaemic cell lines, human placenta, trophoblastic cells, vascular endothelial... 

GM-CSF is undetectable in the serum of normal humans, and no normal cells have been shown to express this protein constitutively. Some transformed cells may constitutively express GM-CSF, and it is actively synthesised and secreted by antigen- and lectin-stimulated T cells and by endothelial cells and fibroblasts exposed to TNF, IL-1 or endotoxin. Other sources of GM-CSF include stimulated B lymphocytes, macrophages, mast cells and osteoblasts, whilst TNF and IL-1 can stimulate its production by acute myeloid leukaemia cells. Some solid tumours and synovial cells from rheumatoid joints may also express GM-CSF and this may be important in disease pathology. 

Jarvis, W.D., Fornari Jr, F.A., Traylor, R.S., Martin, H.A., Kramer, L.B., ErukuUa. R.K., Bittman, R. and Grant, S., 1996, Induction of apoptosis and potentiation of ceramide-mediated cytotoxicity by sphingoid bases in human myeloid leukaemia cells, J. Biol. 

Crowley JA, Wang Y, Rapoport AP, Ning Y (2005) Detection of MOZ-CBP fusion in acute myeloid leukemia with 8 16 translocation. Leukemia 19 2344-2345 Dash A, Gilliland DG (2001) Molecular genetics of acute myeloid leukaemia. Best Pract Res Clin Haematol 14 49-64... 

Murati A, Adelaide J, Mozziconacci MJ, Popovici C, Carbuccia N, Letessier A, Birg F, Birnbaum D, Chaffanet M (2004) Variant MYST4-CBP gene fusion in a t(10 16) acute myeloid leukaemia. Br J Haematol 125 601-604... 

Wiley JS, Cebon JS, Jamieson GP, Szer J, Gibson J, et al. 1994. Assessment of proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF) in acute myeloid leukaemia using a fluorescent ligand for the nucleoside transporter. Leukemia 8 181-185. 

Ralfkiaer, E., Pulford, K. A. F., Lauritzen, A. F., Avnstrom, A., Guldhammer, B., and Mason, D. Y. (1989) Diagnosis of acute myeloid leukaemia with the use of monoclonal anti-neutrophil elastase (NP57) reactive with routinely processed biopsy samples. Histopathol. 14, 637-643. 

Rasoul NA, Elhalawani N, Nafae MH, Elkaffash DM, Moiuad Zl. Telomerase activity in Philadelphia positive chronic myeloid leukaemia. Eg3rpt.J.lnununol. 2004 11 1 8. 

Campbell LJ, Fidler C, Eagleton H et al. hTERT, the catal34ic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia. Leukemia 2006 20 671-679. 

Humanized and chimerized MAbs have been developed for the treatment of non-Hodgkin lymphoma, renal cell carcinoma, ovarian carcinoma, breast cancer, melanoma, and neuroblastoma [117,119,120,123,124]. Patients with relapsed or refractory myeloid leukaemias that have been treated with HuM95, did not develop significant HAMA responses [59]. 

NHL, Non-Hodgkin s lymphoma ALL/CLL, acute/chronic lymphoblastic leukaemia AML, acute myeloid leukaemia. 

Williams RL, Hilton DJ, Pease S, Wilson TA, Stewart CL, Gearing DP, Wagner EF, Metcalf D, Nicola NA, Gough NM. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 1988 336 684-687. 

While filgrastim has proved a useful adjuvant to chemotherapy for many cancers, its administration in cases of myeloid leukaemia would give cause for concern, as these cells express receptors for G-CSF. In such cases, G-CSF could potentially promote accelerated growth of these malignant cells. 

CassUeth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E et al. Chemotherapy compared to autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukaemia in first remission. N Engl J Med 1998 339 1649-56. 

Peggs K, Mckinnon S. Imatinb mesylate - the new gold standard for treatment of chronic myeloid leukaemia. N Engl J Med 2003 348 1048-50. 

Tallman MS, GUfiland DG, Rowe JM. Drug therapy of acute myeloid leukaemia. Blood 2005 106 1154-63. 

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