This research is being done because treatment options are very limited and usually unsuccessful for Acute Myeloid Leukemia (AML) in older individuals, or younger people with disease that has relapsed and/or proven resistant to standard therapy. Subjects are invited to participate in this study that will examine the use of three drugs called Sorafenib (Nexavar), Vorinostat (Zolinza) and Bortezomib (Velcade) for treating acute myeloid leukemia.

Inclusion Criteria:

• A confirmed baseline diagnosis of AML by the revised guidelines of the International Working Group for AML including newly diagnosed, relapsed or refractory disease.
• Poor-risk or complex cytogenetics profile, or deletion of chromosome 5, or deletion of chromosome 7, or positive FLT3-ITD mutation.
• The patient must have discontinued all previous therapies for acute leukemia for at least 14 days and recovered from the acute non-hematologic side effects of the therapy.
• Hydroxyurea to control peripheral blood blast count must be discontinued within 24 hours prior to the initiation of treatment.
• Patients must have an ECOG (Zubrod) performance status of 0-2
• Patients must have adequate hepatic and renal function according to the protocol within one week prior to treatment.
• Female patients must be postmenopausal, surgically sterile or agree to use effective methods of contraception throughout the study.
• Male patients, even if surgically sterilized, must agree to practice effective contraception throughout the study.
• Patients must be able to swallow and tolerate oral medications.

Exclusion Criteria:

• Known central nervous system (CNS) leukemia.
• Diagnosis of acute promyelocytic leukemia (APL).
• Grade >/= 2 peripheral neuropathy.
• Serious illness including, significant ongoing or active infection, New York Heart Association (NYHA) Grade III or IV congestive heart failure, unstable angina or new onset angina or myocardial infarction within the past 6 months, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within past 3 months. Serious medical or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirements.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Active corneal erosions or history of abnormal corneal sensitivity test.
• Known or suspected history of severe hypersensitivity reaction to tyrosine kinase inhibitors, histone deacetylase inhibitors, proteosome inhibitors, boron, or mannitol.
• Female patients who are lactating or have a positive serum pregnancy test within 72 hours of initiation of treatment, or a positive urine pregnancy test on Day 1 before first dose of study drug.
• Concurrent use of other histone deacetylase inhibitors (e.g. valproic acid) are prohibited except for HDAC inhibitors or HDAC-inhibitor like agents used for non-cancer treatment (e.g. epilepsy), where a 14 day washout is allowed.
• Radiation therapy within 3 weeks before randomization.
• Patients with known HIV, or known active hepatitis B or C infections.