Leukaemia, chronic myelogenous

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Hairy cell leukaemia Renal cell carcinoma Basal cell carcinoma Malignant melanoma AIDS-related Kaposi s sarcoma Multiple myeloma Chronic myelogenous leukaemia Non-Hodgkin s lymphoma... 

J. Holm, S. I. Hansen, and J. Lyngbye. High affinity folate finding in chronic myelogenous leukaemia serum, relationship of binding characteristics to activity of disease and binder concentration. Scand. J. Haematol. 26 153-155 (1981). 

Rowley JD. Tetter A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973 243 290-293. 

Shtivelman E, Lifshitz B, Gale RP, Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature 1985 315 550-554. 

Traycoff CM, Halstead B, Rice S et al. Chronic myelogenous leukaemia CD34-r cells exit GO/Gl phases of cell cycle more rapidly than normal marrow CD34+ cells. Br.J.Haematol. 1998 102 759-767. 

Alkylsulphonate Esters. Methanesulfonate esters such as busulfan (7.72) produce clinical remission in chronic myelogenous leukaemia. Busulfan acts through an Sfj2 nucleophilic displacement and presumably crosslinks DNA, since the methanesulfonate... 

Alpha interferon is also effective in the treatment of hairy cell leukaemia, condyloma acuminata (caused by papilloma virus), chronic myelogenous leukaemia and AIDS related Kaposi s sarcoma. 

Cowan-Jacob SW, Fendrich G, Floersheimer A et al. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Crystallogr D Biol Crystallogr 2007 63(Pt l) 80-93. 

Bouchet S et al (2010) Therapeutic drug monitoring of tyrosine-kinase inhibitors in the treatment of chronic myelogenous leukaemia interests and limits. Therapie 65 213-218... 

Chronic lymphocytic leukaemia (CLL) Chronic myelogenous leukaemia (CML) Chlorambucil i prednisolone Fludarabinc... 

Castera L, Kahnsky E, Bedossa P, Tertian G, Buffet C. Macrovesicular steatosis induced by interferon aha therapy for chronic myelogenous leukaemia. Liver 1999 19(3) 259-60. 

A series of arylbenzyl ethers and arylbenzylamines based on combretastatin A-4 was prepared and evaluated for anticancer activity against the K562 human chronic myelogenous leukaemia cell line [39]. Among them, the two benzyl ethers 62 and 64, which have the two aryl groups separated by two atoms, thereby mimicking more closely the arrangement present in Combretastatin A-4 were prepared (Schemes 15 and 16). 

Interferon alfa 2b (interferon alfa-2b [usan] Alferon Intron A Viraferon Sch 30500) is a recombinant (rbe) version, and is extensively used by injection as an anticancer agent to treat hairy cell leukaemia, condylomata acuminata, AIDS-related Kaposi s sarcoma, follicular lymphoma, chronic myelogenous leukaemia, lymph or liver metastases of carcinoid tumour, as an anticancer adjunct in malignant melanoma also, in the maintenance of remission in multiple myeloma chronic active hepatitis B, chronic hepatitis C. 

Cowan-Jacob, S. W, Fendrich, G., Floersheimer, A., Furet, R, Liebetanz, J., Rummel, G., Rheinberger, R, Centeleghe, M., Fabbro, D., Manley, R W. Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia. Acta Cryst. D, 2007, 63, 80-93. 

Retinoids have also been studied for their potential in the treatment of oral leucoplakia [243], the prevention of cancers [244,245], and in the treatment of a leukaemia other than APL [246]. In one study, 13-c/s-retinoic acid was found effective for treatment of oral leucoplakia with 16 out of 24 patients responding positively to the treatment [243]. An average of 63% reduction of skin cancers was observed in 5 patients treated with 13-cis-RA (2 mg/kg daily) over a period of 2 years [244]. After discontinuance of therapy, tumour incidence increased 8.5-fold relative to the frequency during treatment. Similarily, 13-ew-RA treatment at 50-100 mg m day was effective in the prevention of second primary tumours in patients with squamous-cell carcinoma of the head and neck [245], although the retinoid was ineffective in preventing recurrences of the original tumour. Recently, the first effective response to oral RA therapy from a patient with a blast crisis of chronic myelogenous leukaemia (CML-BC) was reported [246]. 

C.B. Lozzio, B. B. Lozzio, E. A. Machado, J. E. Fuhr, S. V. Lair, and E. G. Bamberger, Effects of sodium butyrate on human chronic myelogenous leukaemia cell line K562, Nature, 281 (1979) 709-710. 

An improvement in diabetic control with a reduction in dose of insulin or oral antidiabetics was seen in 6 of 7 diabetics given imat-inib for chronic myelogenous leukaemia. A further patient with type 2 diabetes was able to stop all antidiabetic medication during treatment with imatinib. 

Use of imatinib 400 or 600 mg daily for the treatment of chronic myelogenous leukaemia was associated with improved glyeaemie eontrol in 6 of 7 diabetic patients. This allowed a reduetion in insulin dose in 2 patients and oral antidiabetic drug dosage in 4 patients. A ease report deseribes a 70-year-old woman with type 2 diabetes who needed a reduetion in her insulin dose when she was given imatinib for ehronie myeloid leukaemia. Later, while still taking imatinib, she was able to stop the insulin completely. ... 

Ravandi F et al (1999) Chronic myelogenous leukaemia with pl85(BCR/ABL) expression characteristics and clinical significance. BrJ Haematol 107 581-586 Reusch JE, Klemm DJ (2002) Inhibition of cAMP-response element-binding protein activity decreases protein kinase B/Akt expression in 3T3-L1 adipocytes and induces apoptosis. J Biol Chem 277 1426-1432 Reuther GW et al (1994) Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family. Science 266 129-133... 

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