title: Cell cycle regulation and human leukemias: the role of p16INK4 gene inactivation in the development of human acute lymphoblastic leukemia.
abstract: Recent advances in cancer biology have clearly demonstrated that the development of neoplasms as well as their progression are strictly linked to the alteration of molecular mechanisms controlling the cell division cycle. Among these mechanisms the functional inactivation of two important tumor suppressor genes, namely RB1 and p53, has been widely recognized as a pivotal step in human cancerogenesis. In addition to such well-known genes, a new tumor suppressor gene, mapping on chromosome 9p21, has recently been identified and cloned. Several findings suggest that its loss of function is involved in the initiation and/or progression of an enormous number of different malignancies. This gene, named p16INK4, codifies for a small protein capable of binding to, and thus of inhibiting, some specific cyclin-dependent threonine-serine kinases that represent key enzymatic activities essential for the G1-S transition in mammalian cells. This review will summarize some aspects of the cell cycle control mechanisms, with major emphasis devoted to the role played by this recently characterized inhibitor and to the possible linkage between its inactivation and cancer formation. In particular, we will discuss these aspects in the light of the role of p16INK4 gene inactivation in the development of human acute lymphoblastic leukemias. Indeed this gene seems to be the first, and so far the only tumor suppressor gene consistently altered in specific acute hematological malignancies. Finally, future trends in the investigation of 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
authors.initials: F
authors.lastname: Della Ragione
authors.forename: C
authors.initials: C
authors.lastname: Mercurio
authors.forename: A
authors.initials: A
authors.lastname: Iolascon
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*