Protein Prenylation and Hematological Malignancies

Isoprenylation is a posttranslational modification of proteins in which a farnesyl (15-carbon) or a geranylgeranyl (20-carbon) group is attached to a C-terminal cysteine. Isoprenylation provides a protein with abilities that allow it to interact with cell membrane and with other molecules. Such interactions are essential to the biological functions of a significant number of proteins involved in the signaling of cell growth, differentiation, cytoskeletal function and vesicle trafficking. Thus, isoprenylation is extremely relevant to the development of transformation-related cell phenotypes. There are extensive works in the literature documenting the involvement of prenylated protein or their downstream signaling partners in various aspects of pathogenesis of hematological malignancies. This chapter reviews the importance of isoprenylation and these proteins to the biology of hematological malignancies and analyzes the results of clinical studies evaluating the use of inhibitors of protein prenylation in the treatment of these disorders.

Keywords: Isoprenoids, Protein Prenylation, Ras GTPases, MAPK Pathway, PI3K/PKB/AKT pathway, Inhibitors of HMG-COA Reductase, Farnesyl Transferase Inhibitors, non-Hodgkin‘s lymphoma; Hodgkin‘s lymphoma; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Myeloproliferative Disorders; Polycythemia Vera.