Inclusion Criteria:

• Patients may be untreated or previously treated.
• Age > 18 years
• Able to adhere to study schedule and other protocol requirements
• Unequivocal clinicopathologic diagnosis of myelodysplastic syndrome, non 5q- deletion.
• Patients may have had prior chemotherapy or radiotherapy for another malignancy or myelodysplasia as long as it was completed at least 4 weeks (6 weeks for nitrosureas) prior to initiation of therapy.
• ECOG performance status of 0-2 (Appendix 10.3)
• Life expectancy greater than 3 months
• Total bilirubin ≤ 2.0 mg/dl, ALT and AST ≤ 3 X the upper limit of normal (ULN), creatinine < 2.0 mg/dl all within 28 days prior to enrollment.
• Patients must give voluntary written informed consent and HIPAA authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Absolute neutrophil count > 0.5 x 10 (9)/l
• Platelet count > 30 x 10 (9)/l
• Prior treatment with 5-azacytidine is encouraged, but not required.
• Patients may have had prior treatment for MDS, including single agent lenalidomide or bortezomib.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50mIU/ml within 10-14 days prior to and within 24 hours of prescribing lenalidomide and must commit to abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control,at least 4 weeks before starting taking lenalidomide. FCBP must agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.
• All study participants must be registered into the mandatory RevAssist Program®, and be willing and able to comply with the requirements of RevAssist®.

Exclusion Criteria:

• Ejection fraction < 40%
• Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the consent form.
• Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Patients with major surgery within the 28 days prior to trial enrollment.
• Patients with ≥ Grade 2 peripheral neuropathy or active herpes infection
• Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cirrhosis, chronic obstructive or restrictive pulmonary disease, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrythmia.
• Patients with secondary MDS that require concurrent therapy for the primary cancer diagnosis.
• The development of erythema nodosum as characterized by a desquamating rash while taking thalidomide or similar drugs.
• Patient with hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding. . Lactating females must agree not to breast feed while taking lenalidomide.
• Patient has received an investigational drug within 28 days of enrollment.
• Known hypersensitivity to thalidomide or lenalidomide
• Concurrent use of other anti-cancer agents or treatments.
• Known positive for HIV