الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Since the discovery of CML as a single entity it has been the main concern to many researchers at first towards the epidemiological characteristics and predisposing factors for CML which proved to be insignificant except for radiation, Toluene and cigarette smoking. Then came the breakthrough discovery of Ph Ch. in 1960 and development of new techniques of its discovery and the exposure of its role in the pathogenesis, progression, treatment and prognosis of the disease. The term of cytogentics became broadly used with the introduction of PCR, FISH and QPCR and the identification of the indication and time for each to be done and on what interval to attain the best follow up and ac the best monitoring of the cases to have the optimal response to treatment. But being a progressive triphasic disease with less than satisfactory results with the therapy used including hydroxy urea, interferon alpha and subcutaneous ARA C with the high morbidity and mortality related to stem cell transplant for both the donor and recipient and the rarity in the presence of available matched donors due to the age group of the disease or the unfitness of the recipient came the need for a more direct approach. By the year 2000 the era of targeted therapy deputed with the emergence of tyrosine kinase inhibitors having imatinib mesylate as the first approved member of this family and soon Imatinib 400 mg daily became the gold standard in the therapy of CML. Then came the issue of what to be done with patients resistant to imatinib which was dealt with primarily by elevation of the dose of imatinib to 600 - 800 mg daily and then by the introduction of 2nd generation TKIs as Dasatinib and Nilotinib being more potent as a TKI and also addressing new pathways as SRC and aurora kinase. Both showed more potency and better results than imatinib and the efforts continued to produce Bosutinib as newest 2nd generation TKI with studies being in phase II. Then came the perfect mutation T315I which is resistant to all types of tyrosine kinase inhibitors that are being used now leading to production of new drugs against T315I which are in phase I trials as ON012380, MK-0457, PHA-739358, XL228 and AP24534. Also the use of new lines like farnesyl transferase Inhibitors, homoharringtonine, 5-Aza-2′-Deoxycytidine, heat shock protein 90 inhibitors, arsenic trioxide, proteasome inhibitors, cyclin-dependent kinase inhibitors, tumor suppressor PP2A and histone deacetylase inhibitors are under trials with non proven upper hand over the tyrosine kinase inhibitors. This also led to new updates in HSCT being the only curative therapy with new techniques as Mini transplant and the use of MUD and even autologus stem cell transplant. As regard the issue of continuation of Imatinib the most approved option is continuation of therapy as long as possible even life long but these data are early to be interpreted as the oldest patient on tyrosine kinase inhibitors have not reached 10 years of therapy.