title: Alterations of the cyclin-dependent kinase inhibitor p19 (INK4D) is rare in hematopoietic malignancies.
abstract: Cyclin-dependent kinase inhibitors (CDKIs) can be classified into two groups based on the structure of the proteins. One group includes the p21 (CIP1, WAF1, CAP20), p27 (Kip1), and p57 (Kip2) CDKIs, which contain a homologous amino-terminal cyclin-dependent kinase (cdk) inhibitory domain. The p16 (INK4A), p15 (INK4B), and p18 (INK4C) CDKIs, which have an ankyrin repeat motifs, belong to the other group. The p16 and p15 CDKI genes are very frequently altered in a variety of cancers including hematopoietic malignancies. The p19 (INK4D) gene is a newly cloned CDKI which belongs to the latter group. To determine if p19 genetic alterations play a role in hematopoietic malignancies, we examined DNA from 45 childhood newly diagnosed acute lymphocytic leukemias (ALLs), 30 acute myeloblastic leukemias (AMLs), 10 chronic myelocytic leukemias (CMLs), 45 adult T cell leukemias (ATLs), 70 non-Hodgkin's lymphomas (NHLs), and 20 multiple myelomas (MM) as well as 14 ALL, 20 AML, two ATL, and five lymphoma cell lines. Using Southern blot analysis, one homozygous deletion of the p19 gene was detected in a human immunodeficiency virus (HIV)-related Burkitt-like lymphoma sample. No point mutations in any of the samples were found by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Our investigation suggests that alterations of p19 do not play an important role in the development of most hematopoietic malignancies.
authors.affiliation: Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90048, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shiohara
authors.forename: K
authors.initials: K
authors.lastname: Spirin
authors.forename: J W
authors.initials: JW
authors.lastname: Said
authors.forename: A F
authors.initials: AF
authors.lastname: Gombart
authors.forename: T
authors.initials: T
authors.lastname: Nakamaki
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hatta
authors.forename: R
authors.initials: R
authors.lastname: Morosetti
authors.forename: T
authors.initials: T
authors.lastname: Tasaka
authors.forename: T
authors.initials: T
authors.lastname: Seriu
authors.forename: C
authors.initials: C
authors.lastname: Bartram
authors.forename: C W
authors.initials: CW
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Tomonaga
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured
chemical_list: C493974:CDKN2D protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004273:DNA, Neoplasm