Physiopathogenesis of Hematological Cancer

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The number of new discoveries related to diagnostics and therapeutics of hematological cancer is significant. These have resulted in continuous progress in fundamental knowledge about molecular and ...
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Protein Prenylation and Hematological Malignancies

Pp. 103-121 (19)

Chin Jia Lin and Mirna Alameddine

Abstract

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.

Affiliation:

Department of Pathology University of Sao Paulo School of Medicine. Sao Paulo. Brazil.