Acute myeloid leukaemia

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. 

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. 

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. 

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

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. 

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

Recently two other annexins, namely annexin 1 and annexin 10 have been identified in proteomic screens for genes up-regulated in acute myeloid leukaemia (Lopez-Pedrera et al., 2006). Whether these changes have consequences for disease progression or pathogenesis remains to be seen. 

Pui CH (1991) Epipodophyllotoxin-related acute myeloid leukaemia. Lancet, 338(8780) 1468. 

Gerrard G., Payne E., Baker R.J., Jones D.T., Potter M., Prentice H.G. (2004) Clinical effects and P-glycoprotein inhibition in patients with acute myeloid leukaemia treated with zosuquidar trihydrochloride, daunorubicin and cytarabine, Haematologica 89 782-790. 

CS Scott, M Davey, A Hamilton, DR Norfolk (1986) Seram enzyme concentrations in untreated acute myeloid leukaemia, Blut 52 297-303... 

Karaszi, E. et al. 2001. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br. J. Haematol. 112, 308-314. 

Wong O. 1995. Risk of acute myeloid leukaemia and multiple myeloma in workers exposed to benzene. Occupational and Environmental Medicine 52 380-384. 

Canales MA, Arrieta R, Hernandez-Garcia C, Bustos JG, Aguado MJ, Hernandez-Navarro F. A single apheresis to achieve a high number of peripheral blood CD34+ cells in a lithium-treated patient with acute myeloid leukaemia. Bone Marrow Transplant 1999 23(3) 305. 

Fenton, C. Perry, C. M. Spotlight on gemtuzumab ozogamicin in acute myeloid leukaemia, BioDrugs 2006,20, 137-139. 

Lapidot T, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994 367 645-648. 

Radiophosphorus ( P, sodium radiophosphate) is given i.v. Phosphorus is concentrated in bone and in cells that are dividing rapidly, so that the erythrocyte precursors in the bone marrow receive most of the P-irradiation. The effects are similar to those of whole-body irradiation, and in PRV, P is a treatment option for those > 65 years (acaunulation in the gonads precludes its use in younger patients). The maximum effect on the blood count is delayed 1-2 months after a single dose that usually provides control for 1-2 years. It reduces vascular events and delays progression to myelofibrosis. Excessive depression of the bone marrow including leucocytes and platelets is the main adverse effect, but is seldom serious. Acute myeloid leukaemia occurs more frequently in patients treated with P especially when used in combination with hydroxyurea. 

In acute myeloid leukaemia or lymphatic leukaemia as well as in acute leukaemic episodes in non-Hodgkin lymphoma, involvement of the liver may only be detectable clinically by the presence of hepatomegaly and subicterus. Laboratory parameters usually show slightly elevated transaminase as well as bilirubin values, and distinct cholestasis is occasionally observed. (7) Acute hepatic failure can occur during the course of acute leukaemia, (l, 8,26,65) Histologically, there are massive, yet uniform blast-cell infiltrates these are found mainly within the portal fields in acute lymphatic leukaemia (about 95%) and within the sinusoids in acute myeloid leukaemia (about 75%). Involvement of the liver is of no consequence with regard to the underlying disease and its therapy. Secondary infections require systemic treatment with antibiotics and/or antimycotics. 

Macdonald D, Jiang YZ, Swirsky D, Vulliamy T, MorUla R, Bungey J, Barrett AJ. Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor. Br J Haematol 1991 77(l) 43-9. 

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