Bortezomib and Tipifarnib in MDS.

1. MDS (including the non-proliferative form of CMML, i.e. CMML with a WBC count < 12,0 x 109) /L with < 30% blast cells in the bone marrow and with < 5% circulating blasts);

2. IPSS: Intermediate Risk-2 or High Risk;

3. Age at the time of obtaining informed consent >18 years;

4. WHO performance status 0-2;

5. Receiving no treatment for MDS other than supportive care.

1. IPSS: Low risk and Intermediate-1 category;

2. Candidates for allogeneic stem cell transplantation;

3. Having received a stem cell transplantation (allogeneic or autologous);

4. Vitamine B-12 and folic acid deficiency;

5. HIV-1 positivity;

6. Has known or suspected hypersensitivity or intolerance to VELCADE or ZARNESTRA, or heparin or to Boron or Mannitol;

7. Clinically relevant liver (AST/ALT > 1.5 ULN and bilirubin > 2 mg/dl) or renal insufficiency (ECC <50%);

8. Significant, vascular, pulmonary, gastrointestinal, endocrine, rheumatologic, or metabolic disturbances;

9. Uncontrolled diabetes (if receiving anti-diabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug);

10. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis;

11. Pregnant or breastfeeding;

12. Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3;

13. Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 8 weeks before enrollment;

14. Serious medical or psychiatric illness likely to interfere with participation in this clinical study;

15. Use of enzyme-inducing anticonvulsants (e.g. phenytoin, phenobarbital, carbamazepine). Use of valproate because it acts as a histone deacetylase inhibitor. However, subjects may use other non-enzyme inducing anticonvulsants such as gabapentin or topiramate;

16. Necessity of immunosuppressive drugs, anti-apoptotic agents other than Velcade or Zarnestra, systemic corticosteroids or systemic retinoids, or any cancer therapy other than Velcade or Zarnestra during the treatment portion of this study;

17. Prior exposure to farnesyltransferase inhibitors or proteasome inhibitors;

18. Have received an experimental drug or used an experimental medical device within 8 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study;

19. Hematopoietic growth factor therapy or other disease modulating therapy, including the chronic use of systemic corticosteroids or any use of systemic retinoids within 8 weeks before randomization;

20. Known allergy to imidazol derivatives such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole or terconazole;

21. Pregnant or lactating females
22. Having a desire to have children.