title: A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia.
abstract: Little is known about alterations of cyclin dependent kinase inhibitors p15INK4B, p16INK4A and of MDM2 inhibitor p14ARF due to single nucleotide polymorphisms (SNPs) located within the CDKN2A/B genes and/or neighbouring loci. In order to investigate the potential involvement of such common DNA sequence variants in leukemia susceptibility, an association study was performed by genotyping 23 SNPs spanning the MTAP, CDKN2A/B and CDKN2BAS loci, as well as relative intergenic regions, in a case-control cohort made up of 149 leukemia patients, including Philadelphia positive (Ph(+)) acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) samples, and 183 healthy controls. rs564398, mapping to the CDKN2BAS locus that encodes for ANRIL antisense non-coding RNA, showed a statistically significant correlation with the ALL phenotype, with a risk pattern that was compatible with an overdominant model of disease susceptibility and a OR of 2 (95% CI, 1.20-3.33; p=7.1×10(-3)). We hypothesized that this association reflects the capability of some ANRIL polymorphisms to contribute to its transcription changes responsible for alterations of CDKN2A/B expression profiles, thus leading to abnormal proliferative boosts and consequent increased ALL susceptibility.
authors.affiliation: Department of Hematology and Oncologic Sciences L. and A. Seràgnoli, University of Bologna, Bologna, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Marco
authors.initials: M
authors.lastname: Sazzini
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrari
authors.forename: Alessio
authors.initials: A
authors.lastname: Boattini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lonetti
authors.forename: Cristina
authors.initials: C
authors.lastname: Papayannidis
authors.forename: Vilma
authors.initials: V
authors.lastname: Mantovani
authors.forename: Elena
authors.initials: E
authors.lastname: Marasco
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Donata
authors.initials: D
authors.lastname: Luiselli
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D015331:Cohort Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D022661:RNA, Untranslated