Inclusion Criteria:

1. Diagnosis of Ph-positive (by cytogenetics or FISH) or Bcr-ABL-positive (by PCR) CML
in early chronic phase CML (i.e., time from diagnosis
2. Patients must have received no or minimal prior therapy, defined as prior IFN-α (with or without ara-C) and/or an FDA-approved tyrosine kinase inhibitor
(e.g, dasatinib, nilotinib). Prior use of hydroxyurea or anagrelide is allowed with
no limitations.

3. Age >/=18 years

4. ECOG performance of 0-2.

5. Adequate end organ function, defined as the following: total bilirubin <1.5x ULN,
SGPT <2.5x ULN,creatinine clearance (CrCl) >/= 30 mL/min at screening (calculation
according to Cockroft & Gault formula).

6. Patients must sign an informed consent indicating they are aware of the
investigational nature of this study, in keeping with the policies of the hospital.

7. Women of pregnancy potential must practice an effective method of birth control
during the course of the study, in a manner such that risk of failure is minimized.
Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of
the importance of avoiding pregnancy during trial participation and the potential
risk factors for an unintentional pregnancy. Postmenopausal women must be amenorrheic
for at least 12 months to be considered of non-childbearing potential. In addition,
men enrolled on this study should understand the risks to any sexual partner of
childbearing potential and should practice an effective method of birth control.
Adequate forms of contraception are barrier methods (e.g., condoms, diaphragm), oral,
depo provera, or injectable contraceptives, intrauterine devices, spermicidal jelly
or foam, abstinence, and tubal ligation. Women and men must continue birth control
for the duration of the trial & at least 3 months after the last dose of study drug.

8. **continued from above: All WOCBP MUST have a negative serum or urine pregnancy test
within 7 days prior to first receiving investigational product. If the pregnancy test
is positive, the patient must not receive investigational product and must not be
enrolled in the study.

Exclusion Criteria:

1. NYHA cardiac class 3-4 heart disease

2. Cardiac Symptoms: Patients meeting the following criteria are not eligible: Unstable
angina or myocardial infarction within 3 months; Any history of clinically
significant ventricular arrhythmias (such as ventricular tachycardia, ventricular
fibrillation, or Torsades de pointes); Prolonged QTc interval on pre-entry
electrocardiogram (> 470 msec) on both the Fridericia and Bazett's correction;
Symptomatic congestive heart failure within 3 months prior to first dose of ponatinib
(NYHA class III or IV).

3. Patients with active, uncontrolled psychiatric disorders including: psychosis, major
depression, and bipolar disorders.

4. Pregnant or breast-feeding women are excluded.

5. Patients with history of pancreatitis.

6. Patients in late chronic phase (i.e., time from diagnosis to treatment >6 months), or
blast phase are excluded. The definitions of CML phases are as follows: A. Early
chronic phase: time from diagnosis to therapy time from diagnosis to therapy > 6 months; C. Blastic phase: presence of 30% blasts
or more in the peripheral blood or bone marrow; D. Accelerated phase CML: presence of
any of the following features: Peripheral or marrow blasts 15% or more; Peripheral or
marrow basophils 20% or more; Thrombocytopenia < 100 x 10(9)/L unrelated to therapy;
Documented extramedullary blastic disease outside liver or spleen.

7. **continued from above: E. Clonal evolution defined as the presence of additional
chromosomal abnormalities other than the Ph chromosome has been historically been
included as a criterion for accelerated phase. However, patients with clonal
evolution as the only criterion of accelerated phase have a significantly better
prognosis, and when present at diagnosis may not impact the prognosis at all. Thus,
patients with clonal evolution and no other criteria for accelerated phase will be
eligible for this study.