title: Inactivation of cyclin-dependent kinase inhibitor genes and development of human acute leukemias.
abstract: A large body of evidence has definitely demonstrated that cancer development and/or progression is strictly linked to alterations of molecular mechanisms controlling the cell division cycle. In particular, those aberrations which cause a shortening of G1 phase length and a deregulated S phase entry seem to be very important. Two main tumor suppressor loci, involved in the cell cycle regulation, are frequently altered in human tumors. One is located on 13q14 chromosome and includes the gene coding pRb protein while the other is located on 9p21 chromosome and involves two genes, namely p16INK4A and p15INK4B which belong to the same gene family. While RB1 gene is scarcely altered in hematological tumors, the putative tumor suppressor gene(s) on 9p21 appear(s) to be frequently inactivated in some subtypes of cancers derived from hematopoietic tissues. This manuscript will review the main biochemical aspects of the cell division cycle with major emphasis devoted to the findings regarding the recently characterized small proteic mitotic inhibitors and to their possible role in cancer formation. Particular attention will be paid to the data concerning the incidence of p16INK4A (and p15INK4B) gene(s) inactivation in human acute lymphoblastic leukemias. Indeed, such gene(s) seems to be the main, and until now the unique, tumor suppressor gene consistently altered in this acute hematological cancer diseases. Finally, future directions in studies on the connection between cell cycle control and leukemogenesis will be analyzed.
authors.affiliation: Institute of Biochemistry of Macromolecules, Medical School, Second University of Naples, Italy.
authors.forename: F D
authors.initials: FD
authors.lastname: Ragione
authors.forename: A
authors.initials: A
authors.lastname: Iolascon
mesh_terms: D002352:Carrier Proteins / Q000502:physiology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005544:Forecasting; D005656:Fungal Proteins / Q000502:physiology; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology; D020409:Molecular Motor Proteins; D005810:Multigene Family; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins
chemical_list: C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; C493971:CDKN2C protein, human; C493974:CDKN2D protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C075341:KIP2 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases