Ponatinib - Frontline for Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP)

Study Drug Administration: You will take ponatinib by mouth 1 time every day while you are on study with about a cup (8 ounces) of water. You should not eat within 2 hours before or after taking the drug. You will complete a study diary in which you will record the date and time that you take the study drug each time. If you miss any doses, you will also note this in the study diary. Bring this diary to every study visit, as described below. Study Visits: The tests and procedures for this study have a wide range of time in which they can be done. In general, your schedule of study visits will be as follows: * Weekly in Month 1 * Monthly in Year 1 * Three (3) to 4 times in Year 2 * Two (2) to 3 times in every year after that The study staff will help you schedule your study visits. The following tests and procedures will be performed: * Every 1-2 weeks for the first 4 weeks, then every 4-6 weeks for the first year, then every 3-4 months for the next year, then every 4-6 months after that, blood (about 1/2 tablespoon) will be drawn for routine tests. * Every 3 months for the first year, you will have an ECG. * Every 3 months for the first year, then every 6-12 months after that, you will have a physical exam. * Every 3-4 months for the first year, then every 6-12 months after that, blood (about 2 teaspoons) will be drawn to measure levels of leukemia cells in your body. * Every 3-4 months for the first year, then every 6-12 months for the next 2 years, then every 2-3 years after that, you will have a bone marrow aspirate for genetic testing and to check the status of the disease. Length of Participation: You may continue taking the study drug for up to 5 years. You will be taken off study early if intolerable side effects occur, if the disease gets worse, or if you are unable to follow study directions. Your participation on the study will be over when you have completed the follow-up visit/call. Follow-Up: If you leave the study, you will be called or you will come to the clinic within 30 days to learn about any side effects or symptoms you may be having. If you are called, this call will last about 2-3 minutes. This is an investigational study. Ponatinib is FDA approved to treat patients with certain types of leukemia. Its use in this study is investigational. Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.