protein and was approved in south korea for people resistant to or intolerant of imatinib. bosutinib received us fda and eu european medicines agency approval on 4 september 2012, and 27 march 2013, respectively for the treatment of adults with philadelphia chromosome-positive (ph+) chronic myelogenous leukemia (cml) with resistance, or intolerance to prior therapy. asciminib (scemblix) was approved for medical use in the united states in october 2021. treatment-resistant cml while capable of producing significantly improved responses compared with the action of imatinib, neither dasatinib nor nilotinib could overcome drug resistance caused by one particular mutation found to occur in the structure of bcr-abl1 known as the t315i mutation (in other words, where the 315th amino acid is mutated from a threonine residue to an isoleucine residue). two approaches were developed to the treatment of cml as a result: in 2007, chemgenex released results of an open-label phase 2/3 study (cgx-635-cml-202) that investigated the use of a non bcr-abl targeted agent omacetaxine, administered subcutaneously (under the skin) in patients who had failed with imatinib and exhibited t315i kinase domain mutation. this is a study which is ongoing through 2014. in september 2012, the fda approved omacetaxine for the treatment of cml in the case of resistance to other chemotherapeutic agents. independently, ariad pharmaceuticals, adapting the chemical structures from first and second-generation tk inhibitors, arrived at a new pan-bcr-abl1 inhibitor which showed (for the first time) efficacy against t315i, as well as all other known mutations of the oncoprotein. the drug, ponatinib, gained fda approval in december 2012 for treatment of patients with resistant or intolerant cml. just as with second-generation tk inhibitors, early approval is being sought to extend the use of ponatinib to newly diagnosed cml also. vaccination in 2005, encouraging but mixed results of vaccination were reported with the bcr/abl1 p210 fusion protein in patients with stable disease, with gm-csf as an adjuvant. prognosis before the advent of tyrosine kinase inhibitors, the median survival time for cml patients had been about 3–5 years from time of diagnosis. with the use of tyrosine kinase inhibitors, survival rates have improved dramatically. a 2006 follow-up of 553 patients using imatinib (gleevec) found an overall survival rate of 89% after five years. a 2011 followup of 832 patients using imatinib who achieved a stable cytogenetic response found an overall survival rate of 95.2% after 8 years, which is similar to the rate in the general population. fewer than 1% of patients died because of leukemia progression. epidemiology united kingdom cml accounts for 8% of all leukaemias in the uk, and around 680 people were diagnosed with the disease in 2011. united states the american cancer society estimates that in 2014, about 5,980 new cases of chronic myeloid leukemia were diagnosed, and about 810 people died of the disease. this means that a little over 10% of all newly diagnosed leukemia cases will be chronic myeloid leukemia. the average risk of a person getting this disease is 1 in 588. the disease is more common in men than women, and more common in whites than african-americans. the average age at diagnosis is 64 years, and this disease is rarely seen in children.